Pharmacological evidence for the involvement of endogenous α-MSH-like peptides in peripheral nerve regeneration

The possible involvement of α-MSH-like peptides in the regenerative response of peripheral nerves was investigated with a competitive antagonist of α-MSH, the synthetic hexapeptide [ d-Trp 7, Ala 8, d-Phe 10)α-MSH(6–11)-amide. Subcutaneous administration of the α-MSH antagonist during the first 10 days following sciatic nerve crush significantly decreased functional recovery as measured by the foot flick withdrawal test and the walking pattern analysis. Hypophysectomy delayed both the initial sprouting response and the outgrowth rate after major caudal nerve crush. When hypophysectomized rats were treated with the α-MSH antagonist, a further delay in initial sprouting was observed, whereas the outgrowth rate of nerve fibers was not affected. These results suggest that 1) endogenous α-MSH-like peptides stimulate nerve outgrowth following peripheral nerve injury and 2) α-MSH-like peptides derived from a source other than the pituitary may contribute to the physiological stimulus leading to sprouting.