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Tumour necrosis factor-α, interleukin-1β and interleukin-8 induce persistent mechanical nociceptor hypersensitivity

2002; Lippincott Williams & Wilkins; Volume: 96; Issue: 1 Linguagem: Inglês

10.1016/s0304-3959(01)00433-x

1872-6623

Daniela Sachs, Fernando Q. Cunha, Stephen Poole, Sérgio Henrique Ferreira,

Acupuncture Treatment Research Studies

It has been previously described that daily intraplantar (i.pl.) injections of prostaglandin E2 (PGE2) and dopamine in rats for 14 days cause the development of a persistent mechanical nociceptor hypersensitivity state lasting more than 30 days. Considering that during inflammation, the release of these hyperalgesic agents are mediated by cytokines, we investigated in the present study whether interleukin-1β (IL-1β), IL-8 and tumour necrosis factor-α (TNF-α) are able to induce persistent mechanical nociceptor hypersensitivity. Daily i.pl. administration of TNF-α, IL-1β or IL-8 for 18 days led to persistent mechanical nociceptor hypersensitivity, which lasted at least 30 days after the cessation of treatment. The co-treatment of the animals with IL-1β plus indomethacin, but not with atenolol, prevented the induction of persistent mechanical nociceptor hypersensitivity. The co-treatment of the animals with IL-8 plus atenolol, but not with indomethacin, prevented the induction of persistent mechanical nociceptor hypersensitivity. The daily co-treatment of TNF-α with either indomethacin or atenolol partially inhibited (±50%) the induction of persistent mechanical nociceptor hypersensitivity. However, the combined treatment with indomethacin plus atenolol abolished the induction of the persistent mechanical nociceptive hypersensitivity by TNF-α. A single injection of cytokines in the contralateral paws of the animals with persistent hypersensitivity caused only an acute nociceptive response. This observation, together with the demonstration of undetectable levels of immunoglobulins against TNF-α, IL-1β or IL-8 in the sera of animals after the development of the persistent hypersensitivity induced by those cytokines, indicate that this event is not due to an ongoing immunological response against the cytokines. In conclusion, our results support the suggestion that IL-1β- and IL-8-induced persistent mechanical nociceptor hypersensitivity results from the endogenous release of eicosanoids and sympathetic amines, respectively. However, TNF-α-induced mechanical nociceptor hypersensitivity results from the concomitant endogenous release of eicosanoids and sympathomimetic mediators.