Comparison of efficacy of intra-articular injection of platelet-rich plasma with bupivacaine and steroid combination in chronic shoulder pain.

Shoulder pain is characterized by insidious onset, progressive pain, and loss of active and passive mobility in the glenohumeral joint. It is commonly seen in the age group of 40 to 70 years with a female preponderance. Frozen shoulder, also termed as periarthritis shoulder or adhesive capsulitis of the shoulder, is one of the common causes of shoulder pain and stiffness. There is a limitation in daily activities and impaired sleep quality due to night pain and fatigue, all of which result in significant impairment in the quality of life. Chronic shoulder pain could be due to inflammatory, traumatic, or degenerative etiology. The source of pain may be muscles, tendons, ligaments, or joints constituting the shoulder girdle. In addition, rotator cuff injuries, tendinitis, capsulitis, rheumatoid arthritis, and tumors can also lead to shoulder pain.[ 1 2 3 ] Treatment is aimed primarily at symptom relief, improving joint mobility and function, and optimizing the quality of life. It includes the use of both non-pharmacological and pharmacological interventions. Various non-pharmacological treatment modalities available are self-management programs, strengthening exercises, aerobic exercises, modification in physical activity, heat therapy, ultrasonic massage, manipulation under anesthesia, etc. The pharmacological treatment includes administration of acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs; oral or topical), and opioids (oral or patches).[ 4 5 ] Various interventional modalities available are intra-articular injection of local anesthetics, steroids, saline, platelet-rich plasma (PRP), supra scapular nerve block, erector spinae plane block, arthroscopic surgery, etc. Factors leading to inadequate response to intra-articular injections are inadequate delivery of the drug to the target site and inappropriate post-block activity. An important factor is the technical one, involving the delivery of medication into the intra-articular space. Also, incorrect placement of the needle and drug solution in the soft tissue can cause more discomfort to the patient during and after the procedure.[ 3 6 ] Intra-articular corticosteroid therapy is a well-established treatment for shoulder pain, with its therapeutic effect primarily stemming from its potent anti-inflammatory properties. Corticosteroids interrupt the inflammatory and immune response at multiple stages, reducing vascular permeability and inhibiting the accumulation of inflammatory cells, phagocytosis, neutrophil superoxide production, and the activity of metalloproteases and their activators. They also prevent the synthesis and release of inflammatory mediators such as prostaglandins and cytokines. When local anesthetics are combined with corticosteroids in intra-articular injections for shoulder pain, they are observed to prolong the pain relief provided by the anesthetic, complementing the steroid’s therapeutic effects.[ 7 ] There is growing clinical interest in autologous growth factor therapies, such as the use of PRP. PRP is an autologous concentration of human platelets suspended in a small volume of plasma, with the platelet concentration typically being up to four times higher than the normal level found in healthy blood. The growth factors derived from platelets, stored in the alpha granules, play a crucial role in regulating tissue repair processes. Emerging evidence suggests that, beyond their role in haemostasis, PRP may have regenerative effects on body tissues.[ 2 8 9 10 ]

The demographic profile was comparable in the two groups [ Table 1 ]. Comparison of demographic profiles in the two groups The mean NRS was clinically and statistically comparable at baseline in both groups. There was a significant reduction in NRS in group I as compared to group II at 30 minutes and 2 weeks after the procedure. One month after the procedure, the mean NRS in group II decreased and was found comparable to the mean NRS in group I. However, at 2, 3, and 6 months after the procedure, the mean NRS recorded was significantly lower in group II compared to group I. The variation in pain score was measured at different time intervals in both groups, and when compared to baseline, it was clinically and statistically significant ( P < 0.001). The pain scores were clinically and statistically comparable in the two groups at baseline. In group I, the mean pain score (NRS score) before injection was 8.45 ± 1.05, which decreased to 3.3 ± 1.03 half an hour after injection. Pain score was 2.85 ± 1.75, 2.65 ± 1.42, 3.25 ± 1.71, 3.65 ± 2, and 4.05 ± 1.67 at 2 weeks, 1 month, 2 months, 3 months, and 6 months after injection, respectively. In group II, the mean pain score (NRS score) before injection was 8.9 ± 0.55, which decreased to 7.2 ± 2.16 half an hour after injection. Pain score was 5.9 ± 2.44, 2.75 ± 1.55, 1.65 ± 1.13, 1.65 ± 1.13, and 1.66 ± 2.1 at 2 weeks, 1 month, 2 months, 3 months, and 6 months after injection, respectively [ Figure 2 ]. Comparison of pain scores (Numeric Rating Scale) in the two groups In comparison with the pain score before injection, the variation in pain score at different time intervals after the intervention was clinically and statistically significant ( P < 0.05). When assessing patient satisfaction between the two groups, it was found that the median patient satisfaction score was significantly lower in group II compared to group I at both 30 minutes and 2 weeks following the procedure. However, 1 month after the procedure, the mean patient satisfaction score in group II was statistically similar to that of group I. At 2, 3, and 6 months post-procedure, the mean patient satisfaction score was significantly higher in patients who received intra-articular PRP compared to those who received a local anesthetic and steroid combination. Group I showed a notable decline in positive outcomes over time. While the group started with a high percentage of patients reporting their condition as good (76% at 1/2 hour), this trend did not hold. By the 6-month mark, the number of patients reporting fair and poor outcomes increased, and the positive outcomes of excellent and good had dropped to 20% and 28%, respectively. Group II showed gradual positive results throughout the study period. From the start, a majority of patients reported a poor outcome (68% at 1/2 hour) but a gradual improvement in satisfaction score was seen, which was excellent (68%) at the ned of the 6-month period [ Figure 3 ]. Distribution of patient satisfaction in the two groups The improvement in SPADI score in both groups was clinically and statistically significant score at different time intervals when compared to the SPADI score before intervention. Comparison of mean SPADI scores between the two groups at various intervals was comparable at 30 minutes before the procedure in both groups. The mean SPADI score was significantly lower in group I as compared to group II at 2 weeks following the procedure. One month after the procedure, mean SPADI scores in group I and group II were comparable. However, after 2, 3, and 6 months, the mean SPADI score was significantly better in group II as compared to group I ( P < 0.05) [Figures 4 , 5 ]. Comparison of SPADI scores in the two groups Consort diagram In the current study, all patients in group II required one injection only. However, in group I, one patient required two injections. The interval between the injections was 2 months. The difference between the two groups was statistically not significant ( P > 0.05). No patient required surgery at the conclusion of the 6-month study period. However, a 6-month follow-up may not be long enough to accurately determine the number of patients who may ultimately require surgery. The majority of the patients experienced moderate pain on administration of the injectate (16 out of 25 in group I and 19 out of 25 in group II; P > 0.05). Eight patients in group I, one patient in group II, had mild pain on injection ( P > 0.05). One patient from group I reported severe pain on administration of the injectate. Additionally, five patients in group I reported soreness at the injection site after the injection. No patients in either group reported any increase in pain. The soreness resolved within two to 3 days with the use of cold compresses. No serious side effects associated with the technique or the injectate were observed.

In this study, we compared intra-articular bupivacaine–corticosteroid with PRP in 50 patients with chronic shoulder pain who failed to show satisfactory response to conservative management. Both groups showed significant reductions in pain and disability scores at follow-up. Bupivacaine–corticosteroid provided faster short-term pain relief, while PRP demonstrated sustained benefit up to 6 months. Patient satisfaction was higher in the PRP group, and fewer repeat injections were required. No major complications were observed. Recently, intra-articular injection of PRP has been widely used for the treatment of chronic shoulder pain. PRP is a concentrate of platelets in plasma, which degranulates the alpha granules that contains various growth factors such as platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-β), fibroblast growth factor (FGF), hepatocyte growth factor (HGF), and epithelial growth factor (EGF), and the cytokines that help in the healing of soft tissue.[ 11 ] Throughout the course of this study, there was no escalation in the dosage of pharmacological agents. Patients continued to receive their pre-procedural medications and physical therapy, with the dosage of medications being reduced if clinically appropriate. However, no new analgesic agents, additional peripheral injections, or central injections were introduced during the study period. This approach aligns with the protocols followed by other researchers.[ 2 9 ] Both groups were comparable regarding age, sex, and weight distribution, with no significant difference ( P > 0.05) between the two groups. Similar demographic profiles have been observed in other studies.[ 2 8 9 ] Most of the patients in the present study undergoing treatment presented with right shoulder pain in either group owing to the higher incidence of right-handed dominance. The difference between the two groups was not significant. Range of motion was comparable between the two groups, with only one patient in group I having a normal joint movement. An equal proportion of patients (50%) in group I had osteoarthritis and a normal joint. In contrast, approximately two-thirds of the patients had normal joints in group II. Both the techniques, i.e., intra-articular injection of PRP and intra-articular injection of bupivacaine with corticosteroid, were effective and provided good pain relief to the patients with chronic shoulder pain. The mean NRS was comparable at baseline, with a value of 8.45 and 8.9 for group I and group II, respectively. The mean NRS was significantly lower in patients after 30 minutes of receiving intra-articular injection of bupivacaine and steroid as compared to PRP injection recipients. This difference is because of the faster onset of action of local anesthetics and corticosteroids as compared to PRP, which has an onset of action of 3–4 weeks. A further reduction in the pain scores was observed at a 2-week interval for group I, which was significantly lower than group II at the same interval. Patients receiving intra-articular injection of bupivacaine and steroid combination started experiencing slight pain after 2 months of injection, which was evident by an increase in NRS from 2.65 after the first month follow-up to 3.25 during the second month follow-up. On the contrary, patients receiving intra-articular PRP had improved pain scores after 2 months of the injection. A further increase in NRS at the third and sixth month follow-up in group I patients and a reduction in pain score in group II patients led to the observation that intra-articular corticosteroid in combination with local anesthetics is an effective measure to treat short-term pain, whereas intra-articular PRP injection provides a long-term sustained pain relief. Kumar et al . reported improvement in VAS in both groups receiving intra-articular PRP and triamcinolone till the fourth week. But, intra-articular PRP showed a significant improvement in pain and disability score from the fourth week to the sixth month when compared to triamcinolone. Unlu et al . studied the efficacy of PRP injections in 32 patients with adhesive capsulitis of the shoulder. SPADI and ranges of motion in all directions showed significant improvements with therapy, and the group that took PRP injections showed better improvements, and Visual Analog Scale was found to be better for the PRP group after therapy and the third month. Various other comparative studies assessing the efficacy of intra-articular PRP injection and corticosteroids have shown PRP to be effective and safe in the long term.[ 2 5 8 9 10 11 ] Patient satisfaction was better in group II at the end of the 6-month study period, similar to other studies.[ 2 3 8 6 7 8 9 10 11 12 13 14 15 16 17 18 ] A repeat injection was administered when NRS > 4. Single intra-articular PRP injection was 100% effective, whereas one patient in group I required two injections. In our study, we observed that pain on administration of the injectate was the most common side effect, which was moderate. However, the pain was temporary and was relieved within a few minutes of administration and required no intervention. Both groups showed a reduction in pain scores and improvement in the disability index from baseline, with these benefits being maintained throughout the 6-month follow-up period. The greater improvements observed in the PRP group may be attributed to the potential of PRP to positively influence all stages of tissue healing-namely, the inflammatory, proliferative, and remodeling phases-during the healing of the shoulder joint capsule. Intra-articular PRP injection appears to be an effective treatment for chronic shoulder pain. However, further randomized controlled trials and meta-analyses are needed to confirm the long-term safety and efficacy of PRP. Additionally, for consistent and sustained outcomes, a standardized PRP preparation protocol should be established. This study has several limitations. First, all interventions were performed by a single senior pain physician, meaning the study results may reflect the experience of just one practitioner, which could limit the generalizability of the findings. Second, while the study focused on short-term outcomes, long-term effects need to be evaluated in future research. Trials should aim to assess outcomes up to 1-year post-intervention. Third, the use of imaging modalities was not feasible due to the COVID-19 pandemic, though it is worth noting that the results of the landmark-guided technique were not different from those of ultrasound-guided injection in and the differences observed are small and may not be clinically significant. Overall, the current evidence is subject to several important methodological limitations, which should be considered when interpreting the findings.[ 19 20 ]

Intraarticular injections of the shoulder joint with either PRP or a combination of local anaesthetic and steroid demonstrated significant reduction in pain scores and improvement in disability indices from baseline. The superior outcomes in the PRP group suggest that platelet rich plasma may enhance all stages of tissue healing within the shoulder joint capsule. Nevertheless, larger randomized controlled trials and meta-analysis are warranted to validate its long-term safety and efficacy, and to develop standardized PRP preparation protocols for consistent clinical results. a. What is already known about the topic? Intra-articular injections of the shoulder joint are useful in providing pain relief to patients suffering from chronic shoulder pain b. What new information does this study add? There is a huge scarcity of literature regarding the use of intra-articular administration of platelet-rich plasma in the shoulder joint for chronic shoulder pain. There are no conflicts of interest.

This prospective, randomized, and comparative study received approval from the institutional ethics committee (IEC/Th/19/Anest23) and was registered at clinical trials as CTRI/2021/01/030496. Fifty patients of either sex with an age of more than 20 years and attending a pain clinic with a history, physical examination, and pain pattern consistent with adhesive capsulitis and osteoarthritis of the shoulder, radiological findings corresponding with the patient’s clinical symptoms, and not responding to 6 weeks of conservative treatment were included in the study. Patients with a history of uncontrolled diabetes mellitus, immunodeficiency, infection, or active wound in the shoulder region, recent history of severe trauma to the shoulder or its surgery, treatment with anticoagulants and antiplatelet drugs 10 days before injection, use of NSAIDs 2 days before injection, and history of intra-articular steroid injection in the past 3 months were excluded from the study. After obtaining a detailed clinical history, all patients were subjected to clinical examination in the pain clinic. X-ray/magnetic resonance imaging (MRI) of the affected shoulder joint was reviewed. Use of medications like NSAIDS, aspirin, opioids, etc., was recorded. Complete hemogram with erythrocytic sedimentation rate (ESR), thyroid function tests, blood sugar, and other investigations, as required, were done. After explaining the procedure in detail, informed written consent was obtained from all the patients. Each patient was informed about the Numeric Rating Scale (NRS, 0–10) for assessment of pain before performing the procedure. Computer-generated randomization number table was used to divide the patients into two groups of 25 each. Group I ( n = 25) patients were administered anatomical landmark-guided intra-articular shoulder injection with 3 mL drug solution comprising 3 mL of 0.25% bupivacaine plus 1 mL of triamcinolone (40 mg), and patients in group II ( n = 25) were administered intra-articular shoulder injection with 3 mL of PRP that was prepared by collecting 20 mL of patient’s blood and running it through a centrifuge for 15 minutes at 1600 rpm.[ 6 ] The patients were made to sit with the affected arm resting by their side. The procedure was performed under strict aseptic precautions. A 23 G, 1-inch hypodermic needle was advanced into the shoulder joint using an anterior approach, which was followed by injection of either PRP or bupivacaine and steroid combination [ Figure 1a , b ]. After the procedure, a sterile tape was applied. The patient was observed in the recovery room for 30 minutes. (a)Intra-articular shoulder injection with bupivacaine and steroid combination, (b) Intra-articular shoulder injection with platelet-rich plasma A sample size of 25 patients per group was calculated to achieve 80% power, with a 95% confidence interval and a 5% type I error rate, to detect a difference of 9.6 units in the SPADI score and a two-unit change in the NRS score. The primary outcomes of the study were pain relief, patient satisfaction, and improvement in disability. Secondary outcomes included the need for repeat injections, as well as any side effects and any complications related to the procedure. Assessment of pain was done using the NRS (0-10) half an hour before the administration of injectate and half an hour, 2 weeks, 1 month, 2 months, 3 months, and 6 months after the procedure. Patient satisfaction was assessed at 2 weeks, 1 month, 2 months, 3 months, and 6 months after the intervention on a four-point scale, namely “excellent” when the pain relief was reduced by 75% or more; “good” when the pain relief reported was 50–74%; “fair” when the pain reduced by 25–49%; “poor” when the pain reduction was less than 25% or if there was increase in pain. Pain and disability score was assessed by using a self-administered questionnaire and Shoulder Pain and Disability Index (SPADI). It comprises two dimensions: one for pain and the other for functional activities. All the patients were followed up for a duration of 6 months after the first injection to evaluate for the need of subsequent injections. A repeat injection was given with the same approach that had been followed in the initial sitting in case of inadequate pain relief, which was set at NRS >4 after an interval of 6 weeks. Interventions were limited to a maximum of three in any patient during the study period. Any occurrence of pain during administration of the drug solution, pain at the injection site, local site swelling, or fever, if any, was recorded. Pain during administration of injectate was measured on a four-point scale: 1 for no pain, 2 for mild pain, 3 for moderate pain, and 4 for severe pain. Statistical analysis was conducted using SPSS version 17.0 (IBM SPSS Statistics Inc., Chicago, Illinois, USA). Descriptive statistics, including the mean and standard deviation (SD), were calculated. The Chi-square test was employed to compare sex distribution and patient satisfaction levels between the two groups. The unpaired t -test was used to assess differences in age, pain scores at various time points, changes in pain scores, shoulder pain as measured by the SPADI score, and changes in the SPADI score between the two groups. One-way analysis of variance (ANOVA) was applied to compare changes in pain scores and SPADI scores across different time intervals in both groups. Statistical significance was set at a P value of ≤ 0.05.