Cutaneous inflammation alters nociceptor electrophysiology in guinea pigs but not rats

Laiche  Djouhri; Ahmed  Eliwa; Alghalya  Al-Emadi; Yehia Y.  Hussein; Hissa  Al-Suwaidi; Al-Jouhara  Albaloshi; Ayman   Mustafa; Mohammed Seed Ahmed

doi:10.17305/bb.2025.12195

Authors

Laiche Djouhri Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, Doha, Qatar
Ahmed Eliwa College of Medicine, QU Health, Qatar University, Doha, Qatar https://orcid.org/0009-0008-7316-060X
Alghalya Al-Emadi College of Medicine, QU Health, Qatar University, Doha, Qatar https://orcid.org/0000-0001-5947-3580
Yehia Y. Hussein Department of Orthopedic Surgery, Hamad Medical Corporation, Doha, Qatar https://orcid.org/0000-0003-3523-9241
Hissa Al-Suwaidi College of Medicine, QU Health, Qatar University, Doha, Qatar
Al-Jouhara Albaloshi College of Medicine, QU Health, Qatar University, Doha, Qatar https://orcid.org/0009-0000-5203-9570
Ayman Mustafa Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, Doha, Qatar https://orcid.org/0000-0002-0341-7149
Mohammed Seed Ahmed Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, Doha, Qatar https://orcid.org/0000-0001-7179-9735

DOI:

https://doi.org/10.17305/bb.2025.12195

Keywords:

tissue inflammation, nociception, inflammatory pain, in vivo electrophysiology, nociceptors

Abstract

Inflammatory pain hypersensitivity is believed to result, in part, from increased excitability of nociceptive dorsal root ganglion (DRG) neurons. We previously demonstrated in guinea pigs that hindlimb inflammation induces electrophysiological changes in these neurons, including faster action potential (AP) and afterhyperpolarization (AHP) kinetics. Given that rats and guinea pigs are distinct species with notable differences in genetic composition and physiology, we hypothesized that cutaneous inflammation would have different effects on the electrophysiological properties of nociceptive DRG neurons in rats—the predominant rodent model for pain research. To test this hypothesis, we performed intracellular voltage recordings from DRG neurons (n = 430) in deeply anesthetized, untreated (control) and complete Freund’s adjuvant (CFA)-treated rats and guinea pigs. C-, Aδ-, and Aβ-nociceptors were identified based on their dorsal root conduction velocities (CVs) and responses to natural noxious stimuli. Consistent with our hypothesis, we observed no significant changes in any electrophysiological variables in rat nociceptive neurons four days after CFA-induced hindlimb inflammation. In contrast, guinea pig nociceptors exhibited a significant increase in CV and significant decreases in both AP and AHP durations. The inflammation-induced shortening of absolute and relative refractory periods likely contributes to increased firing frequency in nociceptive nerve fibers, thereby promoting inflammatory pain hypersensitivity. These findings suggest species-specific differences in peripheral neuronal mechanisms underlying inflammatory pain, potentially due to variation in ion channel expression and/or function in DRG neurons between rats and guinea pigs. Given the genetic and metabolic similarities between guinea pigs and humans, further research is warranted to determine whether guinea pigs may serve as a more accurate model of chronic inflammatory pain than rats.