Nerve injury alters the effects of interleukin-6 on nociceptive transmission in peripheral afferents.
Interleukin-6 (IL-6) is markedly upregulated in the peripheral and central nervous systems following nerve injury; however, the functional effects of this are unclear. This study investigates the effect of peripheral interleukin-6 on nociceptive transmission in naive and neuropathic states. Using an in vitro rat skin-nerve preparation, 50 ng interleukin-6 inhibited responses of single nociceptive fibers to noxious heat. A 20-ng sample of interleukin-6 only inhibited heat responses in the presence of soluble interleukin-6 receptors. To examine in vivo effects of peripheral interleukin-6, extracellular recordings from dorsal horn neurons were made in anaesthetised naive, sham-operated and neuropathic (spinal nerve ligated) rats. Peripheral interleukin-6 (40-100 ng) markedly inhibited all naturally evoked neuronal responses in naive rats, yet only neuronal responses to heat in neuropathic rats. Behaviourally, intraplantar administration of interleukin-6 (0.01-1 microg) elicited ipsilateral thermal hypoalgesia in naive rats. Thus, interleukin-6 inhibits normal peripheral nociceptive transmission, yet such anti-nociceptive effects are attenuated following nerve injury in a modality-specific manner.
Flatters
Sarah J L
SJ
Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK. sarah.flatters@mail.mcgill.ca
Fox
Alyson J
AJ
Dickenson
Anthony H
AH
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000344:Afferent Pathways / Q000187:drug effects / Q000293:injuries / Q000502:physiology; D000818:Animals; D006358:Hot Temperature / Q000009:adverse effects; D015850:Interleukin-6 / Q000494:pharmacology*; D008297:Male; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013127:Spinal Nerves / Q000187:drug effects* / Q000293:injuries / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D015850:Interleukin-6