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

TLDR

The delineation of TNFα, IL‑1β, IL‑6, and IL‑8 roles in inflammatory hyperalgesia, together with their inhibition by steroidal anti‑inflammatories, explains the drugs’ mechanism of action. The hyperalgesic activities of IL‑1β, IL‑6, IL‑8, TNFα, and carrageenin were investigated in rats. The study found that IL‑6 activates the IL‑1/prostaglandin pathway but not the IL‑8/sympathetic pathway, whereas TNFα and carrageenin activate both pathways; neutralizing TNFα alone abolishes carrageenin‑induced hyperalgesia, neutralizing IL‑1β, IL‑6, or IL‑8 partially reduces it, and combined neutralization of IL‑1β+IL‑8 or IL‑6+IL‑8 completely blocks the response, demonstrating TNFα’s early and essential role in 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.