Preconditioning with cobalt chloride modifies pain perception in mice

Cobalt chloride (CoCl₂) modifies mitochondrial permeability and has a hypoxic-mimetic effect; thus, the compound induces tolerance to ischemia and increases resistance to a number of injury types. The aim of the present study was to investigate the effects of CoCl₂ hypoxic preconditioning for three weeks on thermonociception, somatic and visceral inflammatory pain, locomotor activity and coordination in mice. A significant pronociceptive effect was observed in the hot plate and tail flick tests after one and two weeks of CoCl₂ administration, respectively (P<0.001). Thermal hyperalgesia (Plantar test) was present in the first week, but recovered by the end of the experiment. Contrary to the hyperalgesic effect on thermonociception, CoCl₂ hypoxic preconditioning decreased the time spent grooming the affected area in the second phase of the formalin test on the orofacial and paw models. The first phase of formalin-induced pain and the writhing test were not affected by CoCl₂ preconditioning. Thus, the present study demonstrated that CoCl₂ preconditioning has a dual effect on pain, and these effects should be taken into account along with the better-known neuro-, cardio- and renoprotective effects of CoCl₂.