Behavioural, histological and cytokine responses during hyperalgesia induced by carrageenan injection in the rat tail

Abstract

We produced experimental inflammatory hyperalgesia by injecting carrageenan into the tail of Sprague–Dawley rats. We compared the rats' voluntary running wheel activity following carrageenan injection into the tail to that after carrageenan injection into the hind paw, the conventional site of inflammation, to identify whether the site of inflammatory-induced hyperalgesia altered voluntary activity. We also measured voluntary running before and after injection of carrageenan or saline into the tail or hind paw, and in separate groups of rats we measured the nociceptive response and the associated pro-inflammatory cytokine profiles following a carrageenan injection into the tail. Female rats were injected intradermally with either 2 mg carrageenan or saline into the dorsal surface of the tail. Withdrawal responses to noxious heat (49 °C water), and punctate mechanical (electronic anaesthesiometer) challenges were recorded in 12 rats for 3 days before and 1 h to 48 h after injection. In a separate group of rats, interleukin (IL)-1β, IL-6, tumour necrosis factor-alpha (TNF-α) and cytokine-induced neutrophil chemoattractant (CINC-1) concentrations were measured in plasma and tail tissue samples taken at the site of injection, 3 h, 6 h and 24 h after injections. Voluntary wheel running was reduced significantly following carrageenan injection into the hind paw compared to that after saline injection into the hind paw. Carrageenan injection into the tail did not result in significant reduction in wheel running compared to that after saline injection into the tail. Both thermal and mechanical hyperalgesia were present after carrageenan injection into the tail ( P < 0.01, ANOVA). The hyperalgesia at the site coincided with significant increases in TNF-α, IL-1β, IL-6 and CINC-1 tissue concentrations, peaking 6 h after carrageenan injection ( P < 0.01, ANOVA). We conclude that carrageenan injection into the tail produces inflammatory hyperalgesia with underlying pro-inflammatory cytokine release, but does not affect voluntary running wheel activity in rats.