Increased conduction velocity of nociceptive primary afferent neurons during unilateral hindlimb inflammation in the anaesthetised guinea-pig.
Decreases in durations of action potentials (C- and Adelta-fibre units) and afterhyperpolarisations (A-fibre units) occur in somata of nociceptive dorsal root ganglion neurons during hindlimb inflammation induced in young guinea-pigs by intradermal injections of Complete Freund's Adjuvant into the ipsilateral leg and foot. Here we present evidence that the single-point conduction velocity (i.e. estimated over a single conduction distance) of these nociceptive neurons is increased during this type of inflammation. The single-point conduction velocities in anaesthetised untreated guinea-pigs (control) were compared with those two and four days after Complete Freund's Adjuvant treatment in two types of experiment. The first involved intracellular voltage recordings from somata of ipsilateral L6 and S1 dorsal root ganglion neurons. Units were classified as C, Adelta or Aalpha/beta on the basis of their dorsal root conduction velocities and characterised as nociceptive, low-threshold mechanoreceptive or unresponsive according to their responses to mechanical and thermal stimuli. Compared with untreated animals, significant increases of 54% for C-fibre nociceptive units and 46% for A-fibre nociceptive units in the medians of dorsal root single-point conduction velocities were found four days after Complete Freund's Adjuvant treatment. These increases were greater at four days than at two days after Complete Freund's Adjuvant. A slight tendency in the same direction (10%) that was not significant was also seen in low-threshold mechanoreceptors four days after treatment, but not after two days. The increased velocities were confirmed with compound action potential recordings from ipsilateral S2 dorsal roots and sural nerves, in treated and control animals. Recordings showed a tendency for increased single-point velocities in C, Adelta and Aalpha/beta waves, with the upper border of the Adelta wave (i.e. the border between Adelta and Aalpha/beta waves) falling at a significantly higher conduction velocity in treated than control animals. This was seen both in S2 dorsal roots and in sural nerves. There was also a significant decrease in the mean electrical threshold for eliciting the C and Adelta components of compound action potentials of both dorsal root and sural nerves during inflammation. No evidence was found for a reduction in utilisation time for any components of the sural nerve compound action potential (C, Adelta or Aalpha/beta). The conduction velocity increases may be due to altered expression or activation/inactivation of certain ion channel types, such as Na(+) channels. The present experiments demonstrate that hindlimb inflammation caused a significant increase in conduction velocity of nociceptive but not of low-threshold mechanoreceptive primary afferent neurons during inflammation, as well as a significant decrease in the mean electrical threshold for eliciting the C and Adelta components of compound action potentials of both dorsal root and sural nerves. These changes, together with the previously described changes in the action potential shape of nociceptive neurons during inflammation, probably reflect alterations in membrane function that contribute to inflammatory hyperalgesia.
Djouhri
L
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Department of Physiology, University of Bristol, Medical School, University Walk, BS8 1TD, Bristol, UK.
Lawson
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SN
D000200:Action Potentials / Q000502:physiology*; D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D005260:Female; D005620:Freund's Adjuvant; D007839:Functional Laterality; D005727:Ganglia, Spinal / Q000502:physiology* / Q000503:physiopathology; D006168:Guinea Pigs; D006614:Hindlimb / Q000294:innervation; D006358:Hot Temperature; D007249:Inflammation / Q000503:physiopathology; D008465:Mechanoreceptors / Q000502:physiology; D018482:Muscle, Skeletal / Q000294:innervation*; D009431:Neural Conduction / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D017288:Pain Threshold; D011930:Reaction Time; D012044:Regression Analysis; D013497:Sural Nerve / Q000502:physiology*
D005620:Freund's Adjuvant