Markedly reduced chronic nociceptive response in mice lacking the PAC(I) receptor

The neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) has been proposed to have a role in nociception. Here we have used the for malin test, thermal laser stimulation and mechanical von Prey stimulation t o investigate possible alteration of PAC(1)(-/-) mice nociceptive behaviour . Our finding, that PAC(1)(-/-) mice have a substantial, 75% decrease in no ciceptive response during the late phase, provides clear evidence that the specific PACAP-recepror PAC(1) is involved in the mediation of nociceptive responses during chronic conditions such as inflammation. PAC(1)(-/-) mice had small or no changes in the response to mechanical and thermal laser sti mulation. This suggests a limited, if any, involvement of PAC(1) in nocicep tion after short-lasting stimuli. Injury-induced changes in DRG neuropeptid e expression were more pronounced in PAC(1)(-/-) mice, implying neuroregula tory functions of PAC(1). NeuroReport 12:2215-2219 (C) 2001 Lippincott Will iams & Wilkins.