Decreased CGRP, but preserved Trk A immunoreactivity in nerve fibres in inflamed human superficial temporal arteries
- aDepartment of Neurology, bDepartment of Ophthalmology, St Bartholomew’s and the Royal London School of Medicine, Royal London Hospital, Whitechapel, London, UK, cNational Hospital for Neurology and Neurosurgery, Queen Square, London, UK, dGenentech, South San Francisco, CA, USA.
- Dr P Anand, Academic Department of Neurology, St Bartholomew’s and the Royal London School of Medicine and Dentistry, The Royal London Hospital, Whitechapel, London E1 1BB, UK. Telephone and fax 0044 171 377 7286; email p.anand{at}mds.qmw.ac.uk
- Received 15 May 1998
- Revised 29 July 1998
- Accepted 23 September 1998
Abstract
The peptidergic sensory innervation of cranial blood vessels may play an important part in vascular head pain. The neuropeptides calcitonin gene-related peptide (CGRP) and substance P in sensory fibres are dependent on nerve growth factor (NGF) produced by the blood vessels, and when released from nerve terminals mediate neurogenic inflammation. NGF is increased in inflamed tissues, and acts via its high affinity receptor trk A on nociceptor fibres to produce hyperalgesia. CGRP and trk A immunoreactive nerve fibres have therefore been studied, for the first time, in inflamed (n=7) and non-inflamed (n=10) temporal arteries biopsied from patients with headache and suspected giant cell arteritis. CGRP immunoreactivity was markedly decreased to absent in adventitial nerve fibres in inflamed regions of vessels, which may reflect secretion from nerve terminals, as CGRP immunoreactivity could still be seen in nerve trunks in periadventitial tissue. Trk A immunoreactive nerve fibres were found in a similar distribution to CGRP containing nerve fibres in non-inflamed vessels, and the trk A immunoreactivity was virtually unchanged in inflamed vessels. The evidence supports a role for NGF related mechanisms in inflammatory vascular head pain. Anti-NGF or anti-trk A agents may represent novel analgesics in this condition.
