Conclusions
This study suggests that spinal HO-1 plays a crucial role in the analgesic effects of calcium channel α2δ ligands through the attenuation of glial activation and endogenous opioid release.
Methods
Neuropathic pain was induced by spared nerve injury (SNI) of the sciatic nerve. The mechanical threshold was tested using the von Frey filaments. The expression of spinal glial markers or other genes was examined using reverse transcription polymerase chain reaction.
Results
Systemic HO-1 inhibition reversed the mechanical antiallodynic effects of pregabalin and gabapentin, although peripheral HO-1 inhibition did not alter the mechanical antiallodynic effects of either pregabalin or gabapentin. Intrathecal injection of SnPP or ZnPP abolished the mechanical antiallodynic effects of pregabalin and gabapentin. Pregabalin and gabapentin increased HO-1, arginase-1, and endogenous opioid precursor preproenkephalin gene expression and decreased the expression of glial markers, interleukin-1β, and inducible nitric oxide synthase. Conclusions: This study suggests that spinal HO-1 plays a crucial role in the analgesic effects of calcium channel α2δ ligands through the attenuation of glial activation and endogenous opioid release.