Viscero-visceral hyperalgesia: characterization in different clinical models

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Patients with co-existing visceral conditions sharing sensory projections, including endometriosis and dysmenorrhea, exhibited enhanced pain symptoms and referred hyperalgesia compared to those with single conditions.

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This study investigated viscero-visceral hyperalgesia by comparing patients with co-existing visceral conditions against those with single conditions across four clinical models. The researchers found that pairs of organs sharing common sensory projections, such as irritable bowel syndrome with dysmenorrhea or endometriosis-associated dysmenorrhea with urinary calculosis, exhibited significantly more intense pain and referred muscle hyperalgesia than either condition alone. Treatment of one condition in these overlapping groups also led to improved symptoms in the other, supporting the hypothesis that sensitization of convergent neurons drives this mutual enhancement of pain. Relevance to endometriosis: listed as one indication for GnRH antagonists, though the paper's main focus is uterine fibroids.

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Abstract

Co-existing algogenic conditions in two internal organs in the same patient may mutually enhance pain symptoms (viscero-visceral hyperalgesia). The present study assessed this phenomenon in different models of visceral interaction. In a prospective evaluation, patients with: (a) coronary artery disease (CAD)+gallstone (Gs) (common sensory projection: T5); (b) irritable bowel syndrome (IBS)+dysmenorrhea (Dys) (T10-L1); (c) dysmenorrhea/endometriosis+urinary calculosis (Cal)(T10-L1); and (d) gallstone+left urinary calculosis (Gs+LCal) (unknown common projection) were compared with patients with CAD, Gs, IBS, Dys or Cal only, for spontaneous symptoms (number/intensity of pain episodes) over comparable time periods and for referred symptoms (muscle hyperalgesia; pressure/electrical pain thresholds) from each visceral location. In patients' subgroups, symptoms were also re-assessed after treatment of each condition or after no treatment. (a) CAD+Gs presented more numerous/intense angina/biliary episodes and more referred muscle chest/abdominal hyperalgesia than CAD or Gs; cardiac revascularization or cholecystectomy also reduced biliary or cardiac symptoms, respectively (0.001<p<0.05). (b) IBS+Dys had more intestinal/menstrual pain and abdomino/pelvic muscle hyperalgesia than IBS or Dys; hormonal dysmenorrhea treatment also reduced IBS symptoms; IBS dietary treatment also improved dysmenorrhea (0.001<p<0.05) while no treatment of either conditions resulted in no improvement in time of symptoms from both. (c) Cal+Dys had more urinary/menstrual pain and referred lumbar/abdominal hyperalgesia than Cal or Dys; hormonal dysmenorrhea treatment/laser treatment for endometriosis also improved urinary symptoms; lithotripsy for urinary stone also reduced menstrual symptoms (0.001<p<0.05). (d) In Gs+LCal, cholecystectomy or urinary lithotripsy did not improve urinary or biliary symptoms, respectively. Mechanisms of viscero-visceral hyperalgesia between organs with documented partially common sensory projection probably involve sensitization of viscero-viscero-somatic convergent neurons.
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Viscero-visceral hyperalgesia: Characterization in different clinical models - Maria Adele Giamberardino - Raffaele Costantini - Giannapia Affaitati - Alessandra Fabrizio - Domenico Lapenna - Emmanuele Tafuri - Andrea Mezzetti Abstract Co-existing algogenic conditions in two internal organs in the same patient may mutually enhance pain symptoms (viscero-visceral hyperalgesia). The present study assessed this phenomenon in different models of visceral interaction. In a prospective evaluation, patients with: (a) coronary artery disease (CAD) + gallstone (Gs) (common sensory projection: T5); (b) irritable bowel syndrome (IBS) + dysmenorrhea (Dys) (T10-L1); (c) dysmenorrhea/endometriosis + urinary calculosis (Cal)(T10-L1); and (d) gallstone + left urinary calculosis (Gs + LCal) (unknown common projection) were compared with patients with CAD, Gs, IBS, Dys or Cal only, for spontaneous symptoms (number/intensity of pain episodes) over comparable time periods and for referred symptoms (muscle hyperalgesia; pressure/electrical pain thresholds) from each visceral location. In patients’ subgroups, symptoms were also re-assessed after treatment of each condition or after no treatment. (a) CAD + Gs presented more numerous/intense angina/biliary episodes and more referred muscle chest/abdominal hyperalgesia than CAD or Gs; cardiac revascularization or cholecystectomy also reduced biliary or cardiac symptoms, respectively (0.001 < p < 0.05). (b) IBS + Dys had more intestinal/menstrual pain and abdomino/pelvic muscle hyperalgesia than IBS or Dys; hormonal dysmenorrhea treatment also reduced IBS symptoms; IBS dietary treatment also improved dysmenorrhea (0.001 < p < 0.05) while no treatment of either conditions resulted in no improvement in time of symptoms from both. (c) Cal + Dys had more urinary/menstrual pain and referred lumbar/abdominal hyperalgesia than Cal or Dys; hormonal dysmenorrhea treatment/laser treatment for endometriosis also improved urinary symptoms; lithotripsy for urinary stone also reduced menstrual symptoms (0.001 < p < 0.05). (d) In Gs + LCal, cholecystectomy or urinary lithotripsy did not improve urinary or biliary symptoms, respectively. Mechanisms of viscero-visceral hyperalgesia between organs with documented partially common sensory projection probably involve sensitization of viscero-viscero-somatic convergent neurons.

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Condition tags

dysmenorrheaendometriosisirritable_bowel_syndrome

MeSH descriptors

Gastrointestinal Diseases Heart Diseases Hyperalgesia Hyperalgesia Pain Threshold Viscera Adolescent Adult Aged Aged, 80 and over Cholecystectomy Cholecystectomy Colonic Diseases, Functional Colonic Diseases, Functional Dysmenorrhea Dysmenorrhea Dysmenorrhea Endometriosis Endometriosis Female

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europepmc
last seen: 2026-09-18T06:10:57.818014+00:00
pubmed
last seen: 2026-05-13T22:17:07.008521+00:00
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