Changes in somatic action potential shape in guinea-pig nociceptive primary afferent neurones during inflammation in vivo.

Abstract

We have examined whether there are changes during inflammation in the membrane properties of nociceptive primary afferent neurones in the guinea-pig that might contribute to hyperalgesia. Inflammation was induced by intradermal injections of complete Freund's adjuvant (CFA) in the left leg. Intracellular voltage recordings were made from the somata of ipsilateral L6 and S1 dorsal root ganglion neurones in anaesthetised untreated guinea-pigs at 2 or 4 days after CFA treatment. 2. Units were classified as C, Adelta or Aalpha/beta on the basis of their dorsal root conduction velocities (CVs). Units with receptive fields on the left leg were characterized as nociceptive, low- threshold mechanoreceptive (LTM) or unresponsive according to their responses to mechanical and thermal stimuli. The shapes of their somatic action potentials (APs) evoked by dorsal root stimulation were recorded. 3. Comparisons of data from nociceptive neurones recorded in CFA treated animals after 2 and 4 days with data from CFA untreated (control) animals showed the following significant changes: in C-fibre nociceptors, decreased AP duration at base, AP rise time and AP fall time, and increased maximum rates of AP rise and fall with no change in afterhyperpolarization measured to 80 % recovery (AHP80); in Adelta-fibre nociceptors, decreased AP duration at base, AP fall time and a reduction in AHP80; and in Aalpha/beta-fibre nociceptors, a decreased AHP80 but no change in AP duration. Apart from a more negative membrane potential and AHP depth below 0 mV in Aalpha/beta nociceptors at 4 days compared with 2 days post-CFA, none of the above variables differed significantly between units recorded 2 or 4 days after CFA. Therefore the two groups were pooled and called CFA2 + 4d. 4. The reduction in AP duration in C-fibre nociceptors was apparent both in high threshold mechanoreceptor and polymodal nociceptors and also in units with either cutaneous or subcutaneous receptive fields. 5. No significant changes in AP duration at base or AHP80 were seen 2 or 4 days after CFA compared with control in either LTM or unresponsive neurones, although some of the latter may have become classified as nociceptors after CFA treatment. 6. The alterations in membrane properties of nociceptors should permit higher discharge frequencies, thus contributing to inflammatory hyperalgesia. They suggest active changes in the expression or activation of cation channels during peripheral inflammation.