Unilateral intramuscular injections of acidic saline produce a bilateral, long-lasting hyperalgesia

This study characterizes an animal model of persistent mechanical hyperalgesia induced by repeated intramuscular injections of low pH saline. Saline at pH 4, 5, 6, or 7.2 was injected twice, 2 to 10 days apart, into the gastrocnemius muscle of rats. To quantify hyperalgesia, paw withdrawal latency to radiant heat (heat hyperalgesia) and withdrawal threshold to mechanical stimuli (mechanical hyperalgesia) were measured. Two unilateral injections of low pH saline, 5 days apart, caused a pH-dependent bilateral mechanical, but not heat, hyperalgesia that lasted 30 days. Injections given 2 and 5 days apart produced a significantly greater mechanical hyperalgesia than injections given 10 days apart. Lidocaine injection into the gastrocnemius muscle or unilateral dorsal rhizotomy, 24 h after the second injection (pH 4), had no effect on the contralateral mechanical hyperalgesia. Minimal histopathology was observed in the injected muscle, and changes were similar between groups injected with pH 4 and pH 7.2. Thus, this new model of widespread, chronic muscle-induced pain is unrelated to tissue damage and is not maintained by continued primary afferent input from the site of injury.