Endogenous interleukin-6 contributes to hypersensitivity to cutaneous stimuli and changes in neuropeptides associated with chronic nerve constriction in mice.
Partial nerve injury is a potential cause of distressing chronic pain for which conventional analgesic treatment with opiates or anti-inflammatory agents is not very effective. Constriction nerve injury, widely used to study neuropathic pain, was shown here to induce interleukin-6 (IL-6) mRNA in a subset of rat primary sensory neurons. When we inflicted chronic nerve constriction on mice with null mutation of the IL-6 gene, the hypersensitivity to cutaneous heat and pressure that is induced in wild-type mice was not evident, the loss of substance P in sensory neurons was excessive and the induction of galanin in central sensory projections was reduced. In additional experiments, intrathecal infusion of IL-6 in rats was shown to stimulate synthesis of galanin in approximately one-third of lumbar dorsal root ganglion neurons. The results of these experiments indicate that endogenous IL-6 mediates some of the hypersensitive responses that characterize peripheral neuropathic pain, and influences two neuropeptides that have been implicated in pain transmission.
Murphy
P G
PG
Department of Physiology, Queen's University, Kingston, Canda K7L 3N63.
Ramer
M S
MS
Borthwick
L
L
Gauldie
J
J
Richardson
P M
PM
Bisby
M A
MA
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002908:Chronic Disease; D005260:Female; D005727:Ganglia, Spinal / Q000293:injuries / Q000378:metabolism; D006941:Hyperesthesia / Q000503:physiopathology*; D015850:Interleukin-6 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009408:Nerve Compression Syndromes / Q000150:complications / Q000378:metabolism / Q000503:physiopathology* / Q000523:psychology; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D010812:Physical Stimulation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000503:physiopathology*; D014947:Wounds and Injuries / Q000209:etiology / Q000378:metabolism / Q000523:psychology
D015850:Interleukin-6; D009479:Neuropeptides; D012333:RNA, Messenger