Your browser doesn't support javascript.
loading
Electrophysiological Alterations Driving Pain-Associated Spontaneous Activity in Human Sensory Neuron Somata Parallel Alterations Described in Spontaneously Active Rodent Nociceptors.
North, Robert Y; Odem, Max A; Li, Yan; Tatsui, Claudio Esteves; Cassidy, Ryan M; Dougherty, Patrick M; Walters, Edgar T.
Afiliación
  • North RY; Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
  • Odem MA; Department of Microbiology and Molecular Genetics, McGovern Medical School at UTHealth, Houston, Texas.
  • Li Y; Department of Anesthesia and Pain Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
  • Tatsui CE; Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
  • Cassidy RM; M.D. Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, Texas.
  • Dougherty PM; Department of Anesthesia and Pain Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
  • Walters ET; Department of Integrative Biology and Pharmacology, McGovern Medical School at UTHealth, Houston, Texas.. Electronic address: edgar.t.walters@uth.tmc.edu.
J Pain ; 23(8): 1343-1357, 2022 08.
Article en En | MEDLINE | ID: mdl-35292377
Neuropathic pain in rodents can be driven by ectopic spontaneous activity (SA) generated by sensory neurons in dorsal root ganglia (DRG). The recent demonstration that SA in dissociated human DRG neurons is associated with reported neuropathic pain in patients enables a detailed comparison of pain-linked electrophysiological alterations driving SA in human DRG neurons to alterations that distinguish SA in nociceptors from SA in low-threshold mechanoreceptors (LTMRs) in rodent neuropathy models. Analysis of recordings from dissociated somata of patient-derived DRG neurons showed that SA and corresponding pain in both sexes were significantly associated with the three functional electrophysiological alterations sufficient to generate SA in the absence of extrinsic depolarizing inputs. These include enhancement of depolarizing spontaneous fluctuations of membrane potential (DSFs), which were analyzed quantitatively for the first time in human DRG neurons. The functional alterations were indistinguishable from SA-driving alterations reported for nociceptors in rodent chronic pain models. Irregular, low-frequency DSFs in human DRG neurons closely resemble DSFs described in rodent nociceptors while differing substantially from the high-frequency sinusoidal oscillations described in rodent LTMRs. These findings suggest that conserved physiological mechanisms of SA in human nociceptor somata can drive neuropathic pain despite documented cellular differences between human and rodent DRG neurons. PERSPECTIVE: Electrophysiological alterations in human sensory neurons associated with patient-reported neuropathic pain include all three of the functional alterations that logically can promote spontaneous activity. The similarity of distinctively altered spontaneous depolarizations in human DRG neurons and rodent nociceptors suggests that spontaneously active human nociceptors can persistently promote neuropathic pain in patients.
Asunto(s)
Palabras clave

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Nociceptores / Neuralgia Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: J Pain Asunto de la revista: NEUROLOGIA / PSICOFISIOLOGIA Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Nociceptores / Neuralgia Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: J Pain Asunto de la revista: NEUROLOGIA / PSICOFISIOLOGIA Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos