Decreased CGRP, but preserved Trk A immunoreactivity in nerve fibres in inflamed human superficial temporal arteries

The peptidergic sensory innervation of cranial blood vessels may play an im portant part in vascular head pain. The neuropeptides calcitonin gene-relat ed peptide (CGRP) and substance P in sensory fibres are dependent on nerve growth factor (NGE) produced by the blood vessels, and when released from n erve terminals mediate neurogenic inflammation. NGF is increased in inflame d tissues, and acts via its high affinity receptor trk a on nociceptor fibr es to produce hyperalgesia. CGRP and trk A immunoreactive nerve fibres have therefore been studied, for the first time, in inflamed (n=7) and non-infl amed (n=10) temporal arteries biopsied from patients with headache and susp ected giant cell arteritis. CGRP immunoreactivity was markedly decreased to absent in adventitial nerve fibres in inflamed regions of vessels, which m ay reflect secretion from nerve terminals, as CGRP immunoreactivity could s till be seen in nerve trunks in periadventitial tissue. Trk A immunoreactiv e nerve fibres were found in a similar distribution to CGRP containing nerv e fibres in non-inflamed vessels, and the trk A immunoreactivity was virtua lly unchanged in inflamed vessels. The evidence supports a role for NGF rel ated mechanisms in inflammatory vascular head pain. Anti-NGF or anti-trk A agents may represent novel analgesics in this condition.