The effect of combination of Gabapentin (GABIX®) with Dextromethorphan (DexAlone®) for reducing CRPS in old patients with distal radius fracture

The effect of combination of Gabapentin (GABIX®) with Dextromethorphan (DexAlone®) for reducing CRPS in old patients with distal radius fracture | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The effect of combination of Gabapentin (GABIX®) with Dextromethorphan (DexAlone®) for reducing CRPS in old patients with distal radius fracture Morteza Gholipour, Seyed Mehdi Hosseini Khameneh, Amin Alizadeh, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7208516/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background : Complex regional pain syndrome (CRPS) is a debilitating complication following fractures, particularly prevalent in elderly patients with distal radius fractures. Gabapentin and NMDA antagonists like Dextromethorphan have shown potential in pain modulation and central sensitization reduction, but their combined efficacy in CRPS prevention remains unclear. Objective : To evaluate the effect of combining Gabapentin (GABIX®) with Dextromethorphan (DexAlone®) versus Gabapentin alone on CRPS incidence, postoperative pain, and functional outcomes in elderly patients undergoing closed reduction and K-wire fixation for distal radius fractures. Methods : This prospective randomized clinical trial included 78 patients aged ≥50 years with AO/OTA type C distal radius fractures treated at Akhtar Hospital (Tehran, 2025–2026). Patients were randomized to receive either GABIX® alone (Group B) or in combination with DexAlone® (Group A) for 10 days postoperatively. CRPS diagnosis was assessed using the Modified Research Diagnostic Criteria at 3 and 6 months. Pain scores (VAS) were recorded weekly until 12 weeks. Functional outcomes were assessed using DASH and Mayo Wrist Score at 3 and 6 months. Results : Both groups were demographically comparable. While Group A showed a lower incidence of CRPS (5% vs 13%), the difference was not statistically significant (P > 0.05). Pain scores (VAS) were significantly lower in Group A during the 6th, 10th, and 12th weeks (P6: 0.004, P10: 0.026, P12: 0.014). No significant difference was observed in DASH scores, but the Mayo Wrist Score significantly improved in Group A at 6 months (P = 0.001). Conclusion : The combination of Gabapentin and Dextromethorphan demonstrated superior pain reduction in the subacute phase following distal radius fracture surgery in elderly patients, though CRPS incidence reduction was not statistically significant. This combination may offer a promising strategy for improving postoperative recovery and quality of life. CRPS Dextromethorphan Gabapentin distal radius fracture elderly pain management NMDA antagonist randomized controlled trial Figures Figure 1 Figure 2 Figure 3 Introduction Complex regional pain syndrome is characterized by disproportionate and excessive pain, sensory abnormalities, vasomotor changes, and motor dysfunction which usually happen after trauma or surgery but can happen spontaneously. CRPS rates are higher in females, the upper extremities, and also near half of CRPS cases induced by fractures ( 1 , 2 ). Distal radius fractures (DRFs) are the most common type of fracture in the upper extremity and often occur in elderly patients with osteoporotic bone after low-energy falls ( 3 , 4 ). CRPS incidence rate after a DRF has been reported near 1% in the general adult population in recent research although it varies wildly in different researches ( 5 – 7 ). Different methods, conditions, and treatments have been studied to evaluate and reduce the rate of CRPS and other complications of DRFs, for example, the use of non-surgical methods, placing K-wires versus volar locked plating, open or closed fixation, psychiatric conditions or oral vitamin C consumption ( 6 , 8 – 10 ). A study in 2009 declared that although the rate of internal fixation of DRF in the elderly increased closed treatment is the predominant method especially in elderly patients are significantly more likely to be treated with closed fixation ( 4 ). There are multiple studies showing Dextromethorphan which is an N-methyl-D-aspartate (NMDA) antagonist can reduce pain intensity at doses of 30–90 mg, decrease the amount of analgesics needed in postoperative patients, enhance primary and secondary thermal hyperalgesia and also improve well-being without major side effects. ( 11 – 14 ). This effect is because of the fact that activation of NMDA receptors due to persistent pain and increased tissue damage causes the spinal cord neuron to become more responsive to its inputs, resulting in central sensitization which is likely contributed to the post-injury pain hypersensitivity states. So, we can assume there is a potential role of NMDA antagonists like Dextromethorphan in pre-emptive analgesia and for treating established pain states.( 15 ) Despite these studies, there are some reports showing Dextromethorphan isn’t able to either reduce postoperative pain intensity or has analgesic- or opioid-sparing effects in orthopedic surgeries( 16 ). Therefore, the primary aim of this study is to evaluate the efficacy of Dextromethorphan in preventing CRPS after distal radius fractures in old patients treated with closed reduction and fixation with K-wire and external fixator. We also measured postoperative pain scores and clinical performance. Material & Methods This is a prospective clinical trial study that was conducted fromJuly 2024 to July 2025 on 85 patients in the age ≥ 50 years who were diagnosed with distal radius fracture type C (AO/OTA) in Akhtar Hospital-Tehran. Fractures of the patients were confirmed by radiography of the wrist series and CT scan. This study was started after the approval of Shahid Beheshti University of Medical Sciences ethics committee and obtaining informed consent from all patients. Demographic information of the patients was extracted from the clinical file. Bone marrow density (BMD) was measured for all patients based on the protocol of the hospital (Akhtar-Tehran). Subjects were labeled and divided into group A and group B using the random sequence generated by the software. All patients were treated with oral medication for 10 days from the second day after surgery. For group A patients, daily combination of GABIX® (Gabapentin 100 mg 1 capsule) with DexAlone® (Dextromethorphan capsules)( 17 ) and for group B patients GABIX® ( 18 )(Gabapentin 100 mg 1 capsule) were prescribed. All patients after regional axillary block were operated by a hand fellowship surgeon. Fixation technique was closed reduction and fixation with K-wire and external fixator. Exclusion criteria included: patients < 50 years of age, diagnosis of sensory and/or motor neuropathy of the upper limb, previous wrist fracture, cardiac and hypertension diseases, neurological disease (Parkinson's, depression and Alzheimer's), systemic diseases (rheumatoid arthritis - lupus erythematosus - scleroderma and vasculitis), bilateral fracture and pathological fracture, associated carpal tunnel syndrome. For all patients, the Proposed Modified Research Diagnostic Criteria for CRPS questionnaire was filled at the end of the second, third and sixth months after surgery. Postoperative pain score using visual analog scale (VAS) ( 19 ) in the first, second, fourth, sixth, tenth, and twelfth weeks after surgery and the results of patients' clinical performance using Mayo Wrist Score (MW)( 20 ) Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire( 21 ) in The third and sixth months after surgery were compared in two groups. All patients underwent physiotherapy and six weeks after surgery removed K-wire and external fixator. The results were presented as mean ± standard deviation (SD) for quantitative variables and were summarized by absolute frequencies and percentages for categorical variables. Categorical variables were compared using chi-square test. Quantitative variables were also compared with t test. Median values of the outcome variable (pain using VAS) between groups were analyzed for statistical significance using the Mann-Whitney U test. For the statistical analysis, the statistical software SPSS version 16.0 for windows (SPSS Inc., Chicago, IL) was used. RESULTS Eighty-five eligible patients were considered for the study. After the entry and exit criteria, 78 patients were selected and randomly divided into groups A (39 patients) and group B (39 patients), (Fig. 1 ).All patients completed six months of follow-up and underwent final analysis. The study included 55 (70.5%) women with an average age of 61.3 ± 4.95 and 23 (29.5%) men with an average age of 62.04 ± 5.03. Both groups were similar in terms of age and sex, proportion of predominant lesions of the hand, and osteoporotic risk and complications after surgery and type of fracture. (P > 0.05), (Table 1 ). Proposed Modified Research Diagnostic Criteria for CRPS was filled at the end of the third and sixth month for both groups. Group A patients had lower CRPS rate during the follow-up period than group B but didn’t showed a statistically significant difference. (P > 0.05). At the end of the study, despite drug and physiotherapy treatment, 2 (5%) patients from group A and 5 (13%) patients from group B were referred to the pain clinic for treatment, (Table 1 ). The pain score between the two groups was compared at the end of the first, second, fourth, sixth, tenth and twelfth weeks after surgery. VAS score in the first, second and fourth week of both groups was similar and no statistically significant difference was observed between the groups (P1:0.099, P2:0.0214, P3:0.443).In the sixth, tenth and twelfth weeks, the pain score in group A was significantly lower than that of group B (P6:0.004, P10:0.026, P12:0.014) (Table 2 ).In the three-month follow-up period, the VAS score showed a statistically significant difference between the groups (P = 0.027), (Fig. 2 ). There was no significant difference in DASH and MWS scores between groups in the third month after surgery (P = 0.486) (Table 3 ). Despite the improvement of clinical results in the sixth month compared to the third month, the DASH score of the patients did not change significantly during the follow-up period (P: 0.147), but the MWS score showed a statistically significant difference during the follow-up period (P: 0.001), (Fig. 3 ). Table 2 Comparison of VAS at different time intervals (N = 78) Variable Group A(N = 39) Group B(N = 39) *P-value VAS-score (1th week) 3.61 ± 1.16 4.12 ± 1.52 0.099 VAS-score (2ndweek) 3.17 ± 1.12 3.48 ± 1.04 0.214 VAS-score (4th week) 2.89 ± 0.94 3.07 ± 1.10 0.443 VAS-score (6th week) 1.94 ± 0.75 2.51 ± 0.91 0.004 VAS-score (10th week) 1.89 ± 0.68 2.25 ± 0.71 0.026 VAS-score (12th week) 1.53 ± 0.64 1.87 ± 0.52 0.014 *P values of 0.05 or less are considered statically significant Table 3 Comparison of DASH score and MHQ score among the different treatment (N = 78) Variable score Group A(N = 39) Group B(N = 39) *P-value DASH (3rd month) 26.22 ± 10.2 26.5 ± 7.86 0.882 DASH (6th month) 17.30 ± 3.51 20.38 ± 4.59 0.001 MWS (3rd month) 80.51 ± 8.14 77.66 ± 10.62 0.188 MWS (6th month) 87.28 ± 6.01 83.07 ± 10.74 0.036 *P values of 0.05 or less are considered statically significant Discussion Complex regional pain syndrome describes an inappropriate continuous regional (not in a specific dermatome) pain with a distal predominance group of abnormal conditions of sensory, motor, sudomotor, vasomotor, and/or trophic findings. ( 2 ) The incidence of CRPS in the general population is reported to be 26.2 per 100,000 person-years. With a higher risk in elderly Females and the highest risk in Postmenopausal women, the incidence rate in females was nearly three times more often than in males. The upper extremity was affected more frequently than the lower extremity and 44% of cases started with a fracture which makes it the most common cause. ( 1 ) Fractures of the distal radius are common in the upper extremity and elderly population, usually caused by low-energy falls ( 3 , 4 ). Complications occur in nearly 30% of patients over 65 years old. The main complication in the conservatively treated group was reported to be malunion, and in the internal fixation group, neuropathies and mechanical failure were common ( 22 ). The CRPS rate post-DRF varies between different studies, as explained below. In our study, six months post-surgery, 7 patients out of 78 patients were diagnosed with CRPS (nearly 9%), we only entered patients above 50 years with type C fracture. CRPS-1 rate after DRF was lower in some studies with an unrestricted inclusion criterion, for instance, in a study on all patients with DRF visiting the emergency unit (88 patients), the estimated CRPS rate was approximately 1% ( 5 ) or in another study with open inclusion criterion, they analyzed South Korea nationwide database with a total number of 172,194 patients, 1,103 CRPS-1 cases were diagnosed(0.64%), and they declared that the incidence of CRPS-1 in age group of 50 s and 60 s was higher than patients in any other age group, but type of fracture wasn’t analyzed( 6 ). Type of fracture can affect the rate of CRPS as in some studies patients with Coln fracture have suffered more from CRPS,( 5 , 23 ) and in other studies, patients with type B and C fractures showed increased risk of developing CRPS( 9 )On the other hand, in other studies rate of CRPS was nearly 20 percent ( 18 ), for example, in a study of the efficiency of vit C on the incidence of CRPS, 18 patients from a total of 119 patients diagnosed with CRPS, in this study Only adult patients with conservatively treated fractures (immobilization by a plaster cast with or without reduction under local anesthesia) were enrolled. We used closed reduction and K- wires, being reported as a favorable method of treatment ( 4 ). Open reduction has been reported to be a risk factor for CRPS ( 6 ). Non operative treatment also showed acceptable outcomes, especially in low-demand elderly patients ( 24 ). We can assume the higher rate of CRPS in this study is related to the medical condition of the patients we evaluated. It must be noted that we excluded patients with rheumatologic diseases which is a risk factor in developing CRPS ( 6 ). The involvement of NMDA receptors in processing sensory afferent signals and maintaining central sensitization which is an underlying mechanism for post-injury hyperalgesia shows the potential of NMDA antagonists as therapeutic agents in managing and preventing chronic pains. NMDA receptor activation leads to a wind-up process of nerve transmission toward brain centers, leading to pain perception. Dextromethorphan binds to receptor sites in the spinal cord and central nervous system, thereby blocking the central transmission of both acute and chronic pain responses to peripheral nociceptive stimuli and subsequently reducing the need for conventional analgesics. At doses ranging from 30 to 90 mg, it attenuates acute pain without significant adverse effects, leading to a decrease in postoperative analgesic consumption in a substantial proportion of patients. Findings indicate that Dextromethorphan also improves overall patient well-being by diminishing sedation but there are studies in secondary pain models in healthy volunteers and various chronic pain states with mixed efficacy, ( 12 , 25 – 27 ). In a more relevant study on 75 patients after surgery for bone and soft tissue malignancies, Dextromethorphan was showed reduced pain intensity, sedation, and analgesic requirements without increasing incidence of side effects ( 28 ). So, although it is not yet completely studied, we could consider Dextromethorphan to be effective in post-operative pain management ( 29 ). 78 patients ultimately fulfilled the inclusion/exclusion criteria and were randomized into two equal groups (n = 39, Group A is a combination of GABIX® with DexAlone®, and Group B is GABIX®+Placebo). There were no meaningful differences in demographic parameters such as age (Group A: 60.92 ± 5.10 years vs. Group B: 60.12 ± 4.79 years), gender distribution, type of fracture, or bone mineral density. In the immediate postoperative phase (1st, 2nd, and 4th weeks), both groups reported similar pain levels, as measured by the Visual Analog Scale (VAS). This may suggest that the acute inflammatory and nociceptive pain following distal radius fracture surgery did not differ between the groups. A divergence in pain scores is seen beginning in the 6th week, with Group A showing lower VAS scores compared to Group B. It suggests Dextromethorphan may aid more in the modulation of subacute or chronic pain mechanisms. Three-month follow-up VAS scores difference (P = 0.027) further supports the long-term efficacy of Dextromethorphan. We measured the Modified Research Diagnostic Criteria for CRPS at both three- and six-months post-surgery. Group A exhibited a lower percentage of CRPS (18% at 3 months and 5% at 6 months) compared to Group B (28% at 3 months and 13% at 6 months), but this difference did not reach statistical significance so we can’t declare Dextromethorphan prevents CRPS but these results indicate better outcomes in Group A which the relatively small numbers and low overall incidence rates may have limited the statistical power to detect a significant difference. Nevertheless, the trend is clinically encouraging, suggesting that Dextromethorphan might play a role in reducing the progression or severity of CRPS. The functional outcome measures showed a promising improvement in group A as discussed below. The Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire was used to evaluate the functional outcome. At three months post-surgery, both groups showed similar results (Group A: 26.22 ± 10.2 vs. Group B: 26.50 ± 7.86, P = 0.882). By six months, however, Group A showed a significantly lower DASH score (17.30 ± 3.51) compared to Group B (20.38 ± 4.59), with a P value of 0.001. The improvement in Group A’s DASH score implies a reduction in upper limb disability and an enhanced performance in daily activities. Mayo wrist scores also showed a similar result. While the MWS of both groups at the three-month follow-up was close (Group A: 80.51 ± 8.14 vs. Group B: 77.66 ± 10.62, P = 0.188), the six-month assessment revealed that Group A had a significantly higher MWS (87.28 ± 6.01) relative to Group B (83.07 ± 10.74, P = 0.036). An improved MWS indicates better overall wrist function, reduced pain and improved objective functional parameters such as range of motion and grip strength. Conclusion CRPS is a complex pain syndrome characterized by persistent, disproportionate pain with accompanying sensory, motor, and autonomic disturbances. It can happen after DHF at variable rates, As it is difficult to treat, studies are focused on preventing it and different treatments have been tested, such as oral Vitamin C. Dextromethorphan is an NMDA receptor antagonist, which showed the potential to reduce pain after different surgeries and also is a safe drug with low-risk side effects. In our study, the combined use of DexAlone® (Dextromethorphan) with GABIX® showed promising trends in reducing subacute and chronic pain. 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Gholipour","email":"data:image/png;base64,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","orcid":"","institution":"Akhtar Hospital","correspondingAuthor":true,"prefix":"","firstName":"Morteza","middleName":"","lastName":"Gholipour","suffix":""},{"id":502153066,"identity":"3f5000df-d75f-4798-b216-0f83dabe29dd","order_by":1,"name":"Seyed Mehdi Hosseini Khameneh","email":"","orcid":"","institution":"Akhtar Hospital","correspondingAuthor":false,"prefix":"","firstName":"Seyed","middleName":"Mehdi Hosseini","lastName":"Khameneh","suffix":""},{"id":502153067,"identity":"69d5293d-2dcb-4e35-8e70-c612d99d80ab","order_by":2,"name":"Amin Alizadeh","email":"","orcid":"","institution":"Akhtar Hospital","correspondingAuthor":false,"prefix":"","firstName":"Amin","middleName":"","lastName":"Alizadeh","suffix":""},{"id":502153068,"identity":"f275af52-ebdb-4fa7-aaf5-5716700135a8","order_by":3,"name":"Fatemeh Abbasi","email":"","orcid":"","institution":"Akhtar Hospital","correspondingAuthor":false,"prefix":"","firstName":"Fatemeh","middleName":"","lastName":"Abbasi","suffix":""}],"badges":[],"createdAt":"2025-07-24 20:08:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7208516/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7208516/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":91842111,"identity":"9af439e4-b567-491a-9439-0c8b6b1a1363","added_by":"auto","created_at":"2025-09-22 09:58:07","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":52630,"visible":true,"origin":"","legend":"\u003cp\u003eThe study flowchart\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7208516/v1/49b22e54dab8db30f41c8363.png"},{"id":91843458,"identity":"e3fcb91b-018b-477d-8012-d7e0fd1690da","added_by":"auto","created_at":"2025-09-22 10:06:07","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":259492,"visible":true,"origin":"","legend":"\u003cp\u003eTrend of pain score (VAS) during the study period between two groups by repeated measurements of ANOVA.*Group A is combination of GABIX® with DexAlone®, and Group B is GABIX®+Placebo.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7208516/v1/50c7425e57893939eb6ee927.png"},{"id":91842110,"identity":"fc520c8c-dcfa-492b-aa30-4ccd10ae7386","added_by":"auto","created_at":"2025-09-22 09:58:07","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":238236,"visible":true,"origin":"","legend":"\u003cp\u003eTrend of MWS and DASH score during the study period between two groups by repeated measurements of ANOVA.*Group A is combination of GABIX® with DexAlone®, and Group B is GABIX®+Placebo.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7208516/v1/3b579ac54d10c1159a004079.png"},{"id":92326598,"identity":"8940fe96-3963-4c26-a572-31035d1a5bfd","added_by":"auto","created_at":"2025-09-27 18:31:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1145701,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7208516/v1/229d6b96-6024-42e8-95ee-c94c386bd210.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The effect of combination of Gabapentin (GABIX®) with Dextromethorphan (DexAlone®) for reducing CRPS in old patients with distal radius fracture","fulltext":[{"header":"Introduction","content":"\u003cp\u003eComplex regional pain syndrome is characterized by disproportionate and excessive pain, sensory abnormalities, vasomotor changes, and motor dysfunction which usually happen after trauma or surgery but can happen spontaneously. CRPS rates are higher in females, the upper extremities, and also near half of CRPS cases induced by fractures (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Distal radius fractures (DRFs) are the most common type of fracture in the upper extremity and often occur in elderly patients with osteoporotic bone after low-energy falls (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). CRPS incidence rate after a DRF has been reported near 1% in the general adult population in recent research although it varies wildly in different researches (\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eDifferent methods, conditions, and treatments have been studied to evaluate and reduce the rate of CRPS and other complications of DRFs, for example, the use of non-surgical methods, placing K-wires versus volar locked plating, open or closed fixation, psychiatric conditions or oral vitamin C consumption (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). A study in 2009 declared that although the rate of internal fixation of DRF in the elderly increased closed treatment is the predominant method especially in elderly patients are significantly more likely to be treated with closed fixation (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThere are multiple studies showing Dextromethorphan which is an N-methyl-D-aspartate (NMDA) antagonist can reduce pain intensity at doses of 30\u0026ndash;90 mg, decrease the amount of analgesics needed in postoperative patients, enhance primary and secondary thermal hyperalgesia and also improve well-being without major side effects. (\u003cspan additionalcitationids=\"CR12 CR13\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). This effect is because of the fact that activation of NMDA receptors due to persistent pain and increased tissue damage causes the spinal cord neuron to become more responsive to its inputs, resulting in central sensitization which is likely contributed to the post-injury pain hypersensitivity states. So, we can assume there is a potential role of NMDA antagonists like Dextromethorphan in pre-emptive analgesia and for treating established pain states.(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) Despite these studies, there are some reports showing Dextromethorphan isn\u0026rsquo;t able to either reduce postoperative pain intensity or has analgesic- or opioid-sparing effects in orthopedic surgeries(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Therefore, the primary aim of this study is to evaluate the efficacy of Dextromethorphan in preventing CRPS after distal radius fractures in old patients treated with closed reduction and fixation with K-wire and external fixator. We also measured postoperative pain scores and clinical performance.\u003c/p\u003e"},{"header":"Material \u0026 Methods","content":"\u003cp\u003eThis is a prospective clinical trial study that was conducted fromJuly 2024 to July 2025 on 85 patients in the age\u0026thinsp;\u0026ge;\u0026thinsp;50 years who were diagnosed with distal radius fracture type C (AO/OTA) in Akhtar Hospital-Tehran. Fractures of the patients were confirmed by radiography of the wrist series and CT scan. This study was started after the approval of Shahid Beheshti University of Medical Sciences ethics committee and obtaining informed consent from all patients. Demographic information of the patients was extracted from the clinical file. Bone marrow density (BMD) was measured for all patients based on the protocol of the hospital (Akhtar-Tehran). Subjects were labeled and divided into group A and group B using the random sequence generated by the software. All patients were treated with oral medication for 10 days from the second day after surgery. For group A patients, daily combination of GABIX\u0026reg; (Gabapentin 100 mg 1 capsule) with DexAlone\u0026reg; (Dextromethorphan capsules)(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e) and for group B patients GABIX\u0026reg; (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e)(Gabapentin 100 mg 1 capsule) were prescribed. All patients after regional axillary block were operated by a hand fellowship surgeon. Fixation technique was closed reduction and fixation with K-wire and external fixator. Exclusion criteria included: patients\u0026thinsp;\u0026lt;\u0026thinsp;50 years of age, diagnosis of sensory and/or motor neuropathy of the upper limb, previous wrist fracture, cardiac and hypertension diseases, neurological disease (Parkinson's, depression and Alzheimer's), systemic diseases (rheumatoid arthritis - lupus erythematosus - scleroderma and vasculitis), bilateral fracture and pathological fracture, associated carpal tunnel syndrome. For all patients, the Proposed Modified Research Diagnostic Criteria for CRPS questionnaire was filled at the end of the second, third and sixth months after surgery. Postoperative pain score using visual analog scale (VAS) (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) in the first, second, fourth, sixth, tenth, and twelfth weeks after surgery and the results of patients' clinical performance using Mayo Wrist Score (MW)(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e) Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e) in The third and sixth months after surgery were compared in two groups. All patients underwent physiotherapy and six weeks after surgery removed K-wire and external fixator.\u003c/p\u003e\u003cp\u003eThe results were presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) for quantitative variables and were summarized by absolute frequencies and percentages for categorical variables. Categorical variables were compared using chi-square test. Quantitative variables were also compared with t test. Median values of the outcome variable (pain using VAS) between groups were analyzed for statistical significance using the Mann-Whitney U test. For the statistical analysis, the statistical software SPSS version 16.0 for windows (SPSS Inc., Chicago, IL) was used.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eEighty-five eligible patients were considered for the study. After the entry and exit criteria, 78 patients were selected and randomly divided into groups A (39 patients) and group B (39 patients), (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).All patients completed six months of follow-up and underwent final analysis. The study included 55 (70.5%) women with an average age of 61.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.95 and 23 (29.5%) men with an average age of 62.04\u0026thinsp;\u0026plusmn;\u0026thinsp;5.03. Both groups were similar in terms of age and sex, proportion of predominant lesions of the hand, and osteoporotic risk and complications after surgery and type of fracture. (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05), (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eProposed Modified Research Diagnostic Criteria for CRPS was filled at the end of the third and sixth month for both groups. Group A patients had lower CRPS rate during the follow-up period than group B but didn\u0026rsquo;t showed a statistically significant difference. (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). At the end of the study, despite drug and physiotherapy treatment, 2 (5%) patients from group A and 5 (13%) patients from group B were referred to the pain clinic for treatment, (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe pain score between the two groups was compared at the end of the first, second, fourth, sixth, tenth and twelfth weeks after surgery. VAS score in the first, second and fourth week of both groups was similar and no statistically significant difference was observed between the groups (P1:0.099, P2:0.0214, P3:0.443).In the sixth, tenth and twelfth weeks, the pain score in group A was significantly lower than that of group B (P6:0.004, P10:0.026, P12:0.014) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).In the three-month follow-up period, the VAS score showed a statistically significant difference between the groups (P\u0026thinsp;=\u0026thinsp;0.027), (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThere was no significant difference in DASH and MWS scores between groups in the third month after surgery (P\u0026thinsp;=\u0026thinsp;0.486) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Despite the improvement of clinical results in the sixth month compared to the third month, the DASH score of the patients did not change significantly during the follow-up period (P: 0.147), but the MWS score showed a statistically significant difference during the follow-up period (P: 0.001), (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cimg 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\"\u003e\u003c/p\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 2\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eComparison of VAS at different time intervals (N\u0026thinsp;=\u0026thinsp;78)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGroup A(N\u0026thinsp;=\u0026thinsp;39)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGroup B(N\u0026thinsp;=\u0026thinsp;39)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e*P-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eVAS-score (1th week)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.61\u0026thinsp;\u0026plusmn;\u0026thinsp;1.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.12\u0026thinsp;\u0026plusmn;\u0026thinsp;1.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.099\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eVAS-score (2ndweek)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.17\u0026thinsp;\u0026plusmn;\u0026thinsp;1.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.48\u0026thinsp;\u0026plusmn;\u0026thinsp;1.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.214\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eVAS-score (4th week)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.89\u0026thinsp;\u0026plusmn;\u0026thinsp;0.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.07\u0026thinsp;\u0026plusmn;\u0026thinsp;1.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.443\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eVAS-score (6th week)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.94\u0026thinsp;\u0026plusmn;\u0026thinsp;0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.51\u0026thinsp;\u0026plusmn;\u0026thinsp;0.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.004\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eVAS-score (10th week)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.89\u0026thinsp;\u0026plusmn;\u0026thinsp;0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.25\u0026thinsp;\u0026plusmn;\u0026thinsp;0.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.026\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eVAS-score (12th week)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.53\u0026thinsp;\u0026plusmn;\u0026thinsp;0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.87\u0026thinsp;\u0026plusmn;\u0026thinsp;0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.014\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003e*P values of 0.05 or less are considered statically significant\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 3\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eComparison of DASH score and MHQ score among the different treatment (N\u0026thinsp;=\u0026thinsp;78)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVariable score\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGroup A(N\u0026thinsp;=\u0026thinsp;39)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGroup B(N\u0026thinsp;=\u0026thinsp;39)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e*P-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDASH (3rd month)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e26.22\u0026thinsp;\u0026plusmn;\u0026thinsp;10.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e26.5\u0026thinsp;\u0026plusmn;\u0026thinsp;7.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.882\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDASH (6th month)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17.30\u0026thinsp;\u0026plusmn;\u0026thinsp;3.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20.38\u0026thinsp;\u0026plusmn;\u0026thinsp;4.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMWS (3rd month)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e80.51\u0026thinsp;\u0026plusmn;\u0026thinsp;8.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e77.66\u0026thinsp;\u0026plusmn;\u0026thinsp;10.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.188\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMWS (6th month)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e87.28\u0026thinsp;\u0026plusmn;\u0026thinsp;6.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e83.07\u0026thinsp;\u0026plusmn;\u0026thinsp;10.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.036\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003e*P values of 0.05 or less are considered statically significant\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n"},{"header":"Discussion","content":"\u003cp\u003eComplex regional pain syndrome describes an inappropriate continuous regional (not in a specific dermatome) pain with a distal predominance group of abnormal conditions of sensory, motor, sudomotor, vasomotor, and/or trophic findings. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) The incidence of CRPS in the general population is reported to be 26.2 per 100,000 person-years. With a higher risk in elderly Females and the highest risk in Postmenopausal women, the incidence rate in females was nearly three times more often than in males. The upper extremity was affected more frequently than the lower extremity and 44% of cases started with a fracture which makes it the most common cause. (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eFractures of the distal radius are common in the upper extremity and elderly population, usually caused by low-energy falls (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Complications occur in nearly 30% of patients over 65 years old. The main complication in the conservatively treated group was reported to be malunion, and in the internal fixation group, neuropathies and mechanical failure were common (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). The CRPS rate post-DRF varies between different studies, as explained below.\u003c/p\u003e\u003cp\u003eIn our study, six months post-surgery, 7 patients out of 78 patients were diagnosed with CRPS (nearly 9%), we only entered patients above 50 years with type C fracture. CRPS-1 rate after DRF was lower in some studies with an unrestricted inclusion criterion, for instance, in a study on all patients with DRF visiting the emergency unit (88 patients), the estimated CRPS rate was approximately 1% (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) or in another study with open inclusion criterion, they analyzed South Korea nationwide database with a total number of 172,194 patients, 1,103 CRPS-1 cases were diagnosed(0.64%), and they declared that the incidence of CRPS-1 in age group of 50 s and 60 s was higher than patients in any other age group, but type of fracture wasn\u0026rsquo;t analyzed(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Type of fracture can affect the rate of CRPS as in some studies patients with Coln fracture have suffered more from CRPS,(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) and in other studies, patients with type B and C fractures showed increased risk of developing CRPS(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)On the other hand, in other studies rate of CRPS was nearly 20 percent (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e), for example, in a study of the efficiency of vit C on the incidence of CRPS, 18 patients from a total of 119 patients diagnosed with CRPS, in this study Only adult patients with conservatively treated fractures (immobilization by a plaster cast with or without reduction under local anesthesia) were enrolled. We used closed reduction and K- wires, being reported as a favorable method of treatment (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Open reduction has been reported to be a risk factor for CRPS (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Non operative treatment also showed acceptable outcomes, especially in low-demand elderly patients (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). We can assume the higher rate of CRPS in this study is related to the medical condition of the patients we evaluated. It must be noted that we excluded patients with rheumatologic diseases which is a risk factor in developing CRPS (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe involvement of NMDA receptors in processing sensory afferent signals and maintaining central sensitization which is an underlying mechanism for post-injury hyperalgesia shows the potential of NMDA antagonists as therapeutic agents in managing and preventing chronic pains. NMDA receptor activation leads to a wind-up process of nerve transmission toward brain centers, leading to pain perception. Dextromethorphan binds to receptor sites in the spinal cord and central nervous system, thereby blocking the central transmission of both acute and chronic pain responses to peripheral nociceptive stimuli and subsequently reducing the need for conventional analgesics. At doses ranging from 30 to 90 mg, it attenuates acute pain without significant adverse effects, leading to a decrease in postoperative analgesic consumption in a substantial proportion of patients. Findings indicate that Dextromethorphan also improves overall patient well-being by diminishing sedation but there are studies in secondary pain models in healthy volunteers and various chronic pain states with mixed efficacy, (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan additionalcitationids=\"CR26\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). In a more relevant study on 75 patients after surgery for bone and soft tissue malignancies, Dextromethorphan was showed reduced pain intensity, sedation, and analgesic requirements without increasing incidence of side effects (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). So, although it is not yet completely studied, we could consider Dextromethorphan to be effective in post-operative pain management (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e78 patients ultimately fulfilled the inclusion/exclusion criteria and were randomized into two equal groups (n\u0026thinsp;=\u0026thinsp;39, Group A is a combination of GABIX\u0026reg; with DexAlone\u0026reg;, and Group B is GABIX\u0026reg;+Placebo). There were no meaningful differences in demographic parameters such as age (Group A: 60.92\u0026thinsp;\u0026plusmn;\u0026thinsp;5.10 years vs. Group B: 60.12\u0026thinsp;\u0026plusmn;\u0026thinsp;4.79 years), gender distribution, type of fracture, or bone mineral density.\u003c/p\u003e\u003cp\u003eIn the immediate postoperative phase (1st, 2nd, and 4th weeks), both groups reported similar pain levels, as measured by the Visual Analog Scale (VAS). This may suggest that the acute inflammatory and nociceptive pain following distal radius fracture surgery did not differ between the groups. A divergence in pain scores is seen beginning in the 6th week, with Group A showing lower VAS scores compared to Group B. It suggests Dextromethorphan may aid more in the modulation of subacute or chronic pain mechanisms. Three-month follow-up VAS scores difference (P\u0026thinsp;=\u0026thinsp;0.027) further supports the long-term efficacy of Dextromethorphan.\u003c/p\u003e\u003cp\u003eWe measured the Modified Research Diagnostic Criteria for CRPS at both three- and six-months post-surgery. Group A exhibited a lower percentage of CRPS (18% at 3 months and 5% at 6 months) compared to Group B (28% at 3 months and 13% at 6 months), but this difference did not reach statistical significance so we can\u0026rsquo;t declare Dextromethorphan prevents CRPS but these results indicate better outcomes in Group A which the relatively small numbers and low overall incidence rates may have limited the statistical power to detect a significant difference. Nevertheless, the trend is clinically encouraging, suggesting that Dextromethorphan might play a role in reducing the progression or severity of CRPS. The functional outcome measures showed a promising improvement in group A as discussed below.\u003c/p\u003e\u003cp\u003eThe Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire was used to evaluate the functional outcome. At three months post-surgery, both groups showed similar results (Group A: 26.22\u0026thinsp;\u0026plusmn;\u0026thinsp;10.2 vs. Group B: 26.50\u0026thinsp;\u0026plusmn;\u0026thinsp;7.86, P\u0026thinsp;=\u0026thinsp;0.882). By six months, however, Group A showed a significantly lower DASH score (17.30\u0026thinsp;\u0026plusmn;\u0026thinsp;3.51) compared to Group B (20.38\u0026thinsp;\u0026plusmn;\u0026thinsp;4.59), with a P value of 0.001. The improvement in Group A\u0026rsquo;s DASH score implies a reduction in upper limb disability and an enhanced performance in daily activities. Mayo wrist scores also showed a similar result. While the MWS of both groups at the three-month follow-up was close (Group A: 80.51\u0026thinsp;\u0026plusmn;\u0026thinsp;8.14 vs. Group B: 77.66\u0026thinsp;\u0026plusmn;\u0026thinsp;10.62, P\u0026thinsp;=\u0026thinsp;0.188), the six-month assessment revealed that Group A had a significantly higher MWS (87.28\u0026thinsp;\u0026plusmn;\u0026thinsp;6.01) relative to Group B (83.07\u0026thinsp;\u0026plusmn;\u0026thinsp;10.74, P\u0026thinsp;=\u0026thinsp;0.036). An improved MWS indicates better overall wrist function, reduced pain and improved objective functional parameters such as range of motion and grip strength.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eCRPS is a complex pain syndrome characterized by persistent, disproportionate pain with accompanying sensory, motor, and autonomic disturbances. It can happen after DHF at variable rates, As it is difficult to treat, studies are focused on preventing it and different treatments have been tested, such as oral Vitamin C. Dextromethorphan is an NMDA receptor antagonist, which showed the potential to reduce pain after different surgeries and also is a safe drug with low-risk side effects.\u003c/p\u003e\u003cp\u003eIn our study, the combined use of DexAlone\u0026reg; (Dextromethorphan) with GABIX\u0026reg; showed promising trends in reducing subacute and chronic pain. Although the reduction in CRPS incidence did not reach statistical significance, the observed improvements in pain scores (VAS) and functional outcomes (DASH and Mayo wrist scores) in the combination therapy group are clinically encouraging. These results may help find adjunctive therapies for DHF treatment by targeting NMDA receptors to enhance postoperative recovery and reduce upper limb disability.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e No funding was obtained for this study.\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003ede Mos M, de Bruijn AGJ, Huygen FJPM, Dieleman JP, Stricker BHC, Sturkenboom MCJM. The incidence of complex regional pain syndrome: A population-based study. Pain [Internet]. 2007 May [cited 2025 Apr 19];129(1\u0026ndash;2):12\u0026ndash;20. Available from: https://journals.lww.com/pain/fulltext/2007/05000/the_incidence_of_complex_regional_pain_syndrome__a.5.aspx\u003c/li\u003e\n\u003cli\u003eGoebel A, Bisla J, Carganillo R, Cole C, Frank B, Gupta R, et al. 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[cited 2025 May 20]; Available from: https://journals.lww.com/pain/abstract/1991/03000/the_induction_and_maintenance_of_central.14.aspx\u003c/li\u003e\n\u003cli\u003eKlepstad P, Maurset A, Moberg E, of I\u0026Oslash;E journal, 1990 undefined. Evidence of a role for NMDA receptors in pain perception. ElsevierP Klepstad, A Maurset, ER Moberg, I \u0026Oslash;yeEuropean journal of pharmacology, 1990\u0026bull;Elsevier [Internet]. [cited 2025 May 20]; Available from: https://www.sciencedirect.com/science/article/pii/001429999090379K\u003c/li\u003e\n\u003cli\u003eWeinbroum AA, Gorodetzky A, Nirkin A, Kollender Y, Bickels J, Marouani N, et al. Dextromethorphan for the reduction of immediate and late postoperative pain and morphine consumption in orthopedic oncology patients. Cancer [Internet]. 2002 Sep 1 [cited 2025 May 22];95(5):1164\u0026ndash;70. Available from: https://onlinelibrary.wiley.com/doi/full/10.1002/cncr.10784\u003c/li\u003e\n\u003cli\u003eRajput R, Al Harakeh K, Figueras G, Mahi A, Minhas M, Sobolevskaia D, et al. Dextromethorphan as an Opioid-Sparing Analgesic in Postoperative Pain. Clin Neuropharmacol [Internet]. 2025 [cited 2025 May 22]; Available from: https://journals.lww.com/clinicalneuropharm/fulltext/9900/dextromethorphan_as_an_opioid_sparing_analgesic_in.121.aspx\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"CRPS, Dextromethorphan, Gabapentin, distal radius fracture, elderly, pain management, NMDA antagonist, randomized controlled trial","lastPublishedDoi":"10.21203/rs.3.rs-7208516/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7208516/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eComplex regional pain syndrome (CRPS) is a debilitating complication following fractures, particularly prevalent in elderly patients with distal radius fractures. Gabapentin and NMDA antagonists like Dextromethorphan have shown potential in pain modulation and central sensitization reduction, but their combined efficacy in CRPS prevention remains unclear.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eTo evaluate the effect of combining Gabapentin (GABIX®) with Dextromethorphan (DexAlone®) versus Gabapentin alone on CRPS incidence, postoperative pain, and functional outcomes in elderly patients undergoing closed reduction and K-wire fixation for distal radius fractures.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eThis prospective randomized clinical trial included 78 patients aged ≥50 years with AO/OTA type C distal radius fractures treated at Akhtar Hospital (Tehran, 2025–2026). Patients were randomized to receive either GABIX® alone (Group B) or in combination with DexAlone® (Group A) for 10 days postoperatively. CRPS diagnosis was assessed using the Modified Research Diagnostic Criteria at 3 and 6 months. Pain scores (VAS) were recorded weekly until 12 weeks. Functional outcomes were assessed using DASH and Mayo Wrist Score at 3 and 6 months.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eBoth groups were demographically comparable. While Group A showed a lower incidence of CRPS (5% vs 13%), the difference was not statistically significant (P \u0026gt; 0.05). Pain scores (VAS) were significantly lower in Group A during the 6th, 10th, and 12th weeks (P6: 0.004, P10: 0.026, P12: 0.014). No significant difference was observed in DASH scores, but the Mayo Wrist Score significantly improved in Group A at 6 months (P = 0.001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eThe combination of Gabapentin and Dextromethorphan demonstrated superior pain reduction in the subacute phase following distal radius fracture surgery in elderly patients, though CRPS incidence reduction was not statistically significant. This combination may offer a promising strategy for improving postoperative recovery and quality of life.\u003c/p\u003e","manuscriptTitle":"The effect of combination of Gabapentin (GABIX®) with Dextromethorphan (DexAlone®) for reducing CRPS in old patients with distal radius fracture","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-22 09:58:03","doi":"10.21203/rs.3.rs-7208516/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4970434f-e3f1-4b97-a52d-95579c7f56b9","owner":[],"postedDate":"September 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-09-27T18:23:26+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-22 09:58:03","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7208516","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7208516","identity":"rs-7208516","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}