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The neurophysiological basis of stress and anxiety - comparing neuronal diversity in the bed nucleus of the stria terminalis (BNST) across species

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
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.3389/fncel.2023.1225758

Authors

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Institution:
University of Oxford
Role:
Author
ORCID:
0000-0001-9787-3307


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Funder identifier:
10.13039/100010269
More from this funder
Funder identifier:
10.13039/501100000265


Publisher:
Frontiers Media
Journal:
Frontiers in Cellular Neuroscience More from this journal
Volume:
17
Pages:
1225758-1225758
Article number:
1225758
Publication date:
2023-08-30
DOI:
EISSN:
1662-5102
ISSN:
1662-5102


Language:
English
Keywords:
Pubs id:
1968111
Local pid:
pubs:1968111
Source identifiers:
W4386329692
Deposit date:
2026-06-10
ARK identifier:
This ORA record was generated from metadata provided by an external service. It has not been edited by the ORA Team.

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