Reduction of formalin-evoked responses and maintenance of peripheral antinociception by morphine against formalin in the spared nerve injury model

This study examined (a) the effect of formalin administration into two different sensory fields, the lateral and medial hindpaw, in the spared nerve injury (SNI) model in rats and (b) peripheral antinociception by morphine when co-administered with formalin at lateral and medial hindpaw sites. Following SNI and injections into the lateral hindpaw, the site most commonly used to evaluate sensory changes using this model, flinching responses to formalin (0.5%, 1%) were unchanged. In contrast, following medial plantar hindpaw injections, flinching responses to formalin (1%, 2.5%) were significantly reduced. When morphine was co-administered with formalin, it exhibited similar peripheral antinociception at both lateral and medial sites, and following sham or SNI surgery. These results indicate that the effects of SNI on chemogenic signaling by formalin, which is now known to involve TRPA1 receptors, differ from effects on allodynia responses. Furthermore, the maintenance of peripheral actions of morphine at both sites supports the notion of exploring peripheral delivery of opioids for pain relief following nerve injury.

► Spared nerve injury reduced formalin-evoked responses at medial hindpaw sites (77 spaces). ► Nerve injury produces a different effect on formalin compared to mechanical allodynia (85 spaces). ► Morphine retains peripheral antinociceptive action against formalin (67 spaces).