Nerve injury alters the effects of interleukin-6 on nociceptive transmission in peripheral afferents

• Published in: European journal of pharmacology 2004-01, Vol.484 (2), p.183-191
• Main Authors: Flatters, Sarah J.L., Fox, Alyson J., Dickenson, Anthony H.
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Action Potentials - physiology; Afferent Pathways - drug effects; Afferent Pathways - injuries; Afferent Pathways - physiology; Animals; Biological and medical sciences; C-fibre; Cytokine; Dorsal horn; Electrophysiology; Hot Temperature - adverse effects; Interleukin-6; Interleukin-6 - pharmacology; Male; Medical sciences; Pain; Pain Measurement - drug effects; Pain Measurement - methods; Peripheral Nerve Injuries; Peripheral Nerves - drug effects; Peripheral Nerves - physiology; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Spinal Nerves - drug effects; Spinal Nerves - injuries; Spinal Nerves - physiopathology; Synaptic Transmission - drug effects; Synaptic Transmission - physiology
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2003.11.013

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 μg) 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.