The pivotal role of tumour necrosis factor α in the development of inflammatory hyperalgesia

Abstract

The hyperalgesic activities in rats of interleukin‐1β (IL‐1β), IL‐6, IL‐8, tumour necrosis factor α (TNFα) and carrageenin were investigated. IL‐6 activated the previously delineated IL‐1/prostaglandin hyperalgesic pathway but not the IL‐8/sympathetic mediated hyperalgesic pathway. TNFα and carrageenin activated both pathways. Antiserum neutralizing endogenous TNFα abolished the response to carrageenin whereas antisera neutralizing endogenous IL‐1β, IL‐6 and IL‐8 each partially inhibited the response. The combination of antisera neutralizing endogenous IL‐1β + IL‐8 or IL‐6 + IL‐8 abolished the response to carrageenin. These results show that TNFα has an early and crucial role in the development of inflammatory hyperaglesia. The delineation of the roles of TNFα, IL‐1β, IL‐6 and IL‐8 in the development of inflammatory hyperalgesia taken together with the finding that the production of these cytokines is inhibited by steroidal anti‐inflammatory drugs provides a mechanism of action for these drugs in the treatment of inflammatory hyperalgesia.

Modulation of ultraviolet‐induced hyperalgesia and cytokine upregulation by interleukins 10 and 13

“…Furthermore, the key role of each of these factors in the induction of in¯ammatory hyperalgesia has also been demonstrated (Andreev et al, 1995;Cunha et al, 1992;Ferreira et al, 1988;Lewin & Mendell ,1993).…”

“…Subsequent studies have established the contribution of neuropeptides (Substance P, CGRP) in the in¯ammatory reaction induced by UVR (Benrath et al, 1995;Gillardon et al, 1992;Scholzen et al, 1999). Furthermore, cytokines and nerve growth factor (NGF), increased during UVB-induced in¯ammation, have been shown to produce hyperalgesia following either local or systemic injections (Andreev et al, 1995;Cunha et al, 1992;Ferreira et al, 1988;Lewin & Mendell 1993;Watkins et al, 1994).…”

An electronic pressure-meter nociception paw test for rats

“…This test was instrumental in the discovery of various seminal findings, which were later confirmed by other nociceptive methods such as formalin-induced flinches (10,11), chemically induced writhing (12,13) and the classical Randall and Selitto method (14). In fact, the modified Randall and Selitto test was used in several pioneering studies of inflammatory nociceptor sensitization (hypernociception): the participation of the cAMP/Ca 2+ pathway in the mechanism of hypernociception (15), the peripheral effect of opiates (16), the cytokine cascade involved in the onset of inflammatory hypernociception (17)(18)(19)(20)(21)(22)(23)(24), the peripheral memory of nociceptor sensitization (25,26), and the spinal retrograde sensitization of primary sensory neurons (27).…”

Physiologic Advantages of Peripheral Nerve Blockade Translate to Decreased Length of Stay and Improved Patient Satisfaction

“…Pro-inflammatory cytokines are involved at the site of inflammation, in the dorsal root ganglion, and within the spinal cord, resulting in neurogenic pain. [31][32][33][34][35] After a tissue stressor, such as surgical insult or trauma, leukocytes are activated and migrate into the circulation. These leukocytes gather at the site of inflammation, causing the release of cytokines, resulting in a more robust local immune responss.…”