Proceedings of The Physiological Society
King's College London (2011) Proc Physiol Soc 22, PC23
Chronic hindlimb inflammation increases excitability of C-, but not A??-, fibre nociceptive neurons in rats in vivo
L. Djouhri1, X. Weng1
1. University of Liverpool, Liverpool, United Kingdom.
Hypersensitivity to painful stimuli (hyperalgesia) and/or normally non-painful stimuli (allodynia) is a hallmark of inflammation. This inflammatory pain hypersensitivity is partly due to sensitization of primary afferent dorsal root ganglion (DRG) neurons. These sensitized neurons exhibit increased spontaneous activity (SA) and decreased activation threshold (Woolf & Ma, 2007). Previous studies have shown increased proportions of both C-and Aδ-fibre nociceptors with SA following acute inflammation (Koltzenburg et al., 1999, Xu et al., 2000). More recently we have shown that the proportion of Aδ-fibre nociceptors showing SA was greater than that of C-fibre nociccetors at both 1 and 4 days after CFA (Complete Freund’s Adjuvant)-induced hindlimb inflammation (Djouhri et al., 2006). Here we examined the impact of CFA-induced chronic inflammation (5-7 days post CFA) on excitability of C-and Aδ-fibre nociceptors innervating inflamed tissue. Hindlimb inflammation was induced by two intradermal injections of 150μl of CFA into the left hindlimb of Wistar rats (one into the plantar surface of teh hindpaw and the other into the knee region). This was to induce inflammation in the whole hindlimb as described previously (Djouhri et al., 2006). Intracellular recordings of somatic action potentials evoked by dorsal root electical stimulation were made from L4/L5 DRG neurons in untreated (control) and CFA treated rats deeply anaesthetised with sodium pentobarbitone (60 mg/kg, i.p). C-and Aδ-fibre nociceptors were identified on the basis of their dorsal root conduction velocities and their responses to noxious mechanical and thermal stimuli. We found that long term inflammation (5-7 days post CFA) increased excitability of C-, but not Aδ-fibre nociceptors as indicated by an afterdischarge response (response that outlasts the stimulus duration) to a brief noxious stimulus (pinch with toothed forceps), increased incidence of SA, and decreased electrical (dorsal root) threshold. Indeed compared to controls, C-fibre nociceptors of CFA-treated rats exhibited a highly significant decrease in electrical threshold (P<0.001, Mann- Whitney U test) and a significant increase in the incidence of SA (P<0.05 Fisher’s exact test). The percentage of SA increase was from 5% (2/43) to 24% (12/50%). Furthermore, 28% of C-nociceptors in CFA rats exhibited afterdischarge responses to a brief noxious pinch. In contrast, Aδ-nociceptors showed no afterdischarge responses, no significant change in the electrical threshold and no SA (0% in control (n=15) vs 0% in CFA, n=12). These results suggest that C-nociceptors contribute more to chronic inflammatory hypersensitivity that Aδ-fibre nociceptors.
Where applicable, experiments conform with Society ethical requirements