Persistent hindpaw inflammation produces coeruleospinal antinociception in the non-inflamed forepaw of rats

Abstract

In a rat model of unilateral hindpaw inflammation, it is unclear whether the coeruleospinal modulation system is active at spinal segments distant from the inflamed plantar region, such as the cervical segments. To clarify this query, in the present study we measured paw withdrawal latency (PWL) to thermal stimuli on four paws (both forepaws and both hindpaws) following induction of inflammation and compared PWLs between rats with bilateral lesions of the locus coeruleus/subcoeruleus (LC/SC) and rats with sham operation. Unilateral hindpaw inflammation was produced by a subcutaneous injection of carrageenan (2 mg in 0.15 ml saline). Prior to carrageenan injection, in all four paws, PWLs did not differ between the LC/SC-lesioned and the sham-operated rats. Four hours after carrageenan injection, PWLs in the inflamed left hindpaw decreased significantly in both the LC/SC-lesioned and the sham-operated rats. The decreased PWLs of the LC/SC-lesioned group were significantly shorter than those of the sham-operated group. These phenomena which were observed in the inflamed left hindpaw were also observed in the non-inflamed left forepaws. In the right forepaws and the right hindpaws, no significant change in PWL was observed between before and 4 h after injection in both the sham-operated and the LC/SC-lesioned rats. These results suggest that unilateral hindpaw inflammation activates the coeruleospinal modulation system and that this modulation system is active not only at the lumbar segments but also at the cervical level where spinal segments are distant from the inflamed plantar region.