Light-aversion and cephalic allodynia in an intravenous CGRP model of migraine-like behaviour in male and female rats
Abstract
BACKGROUND: Photophobia is a common and highly bothersome migraine-associated symptom, where light may cause discomfort and exacerbate headache pain. Calcitonin gene-related peptide (CGRP) may be involved in nociceptive signalling during photophobia. In clinical provocation studies, intravenous CGRP induces both migraine attacks and photophobia. Animal studies attempting to model this have used intraperitoneal or intracranial injections and behavioural tests requiring very high light intensities to provoke light-aversive behaviour, a surrogate for photophobia-like responses. Here, we evaluated the effects of intravenous CGRP on light aversion alongside periorbital sensitivity in naïve rats. METHODS: Male and female Sprague Dawley rats received intravenous injections of 100 µg/kg human αCGRP or saline (n = 6–12/group). After 20 min, light aversion was assessed in an optimized light/dark box (LDB) test. The LDB was optimized by adding bedding material to minimize novelty-related anxiety. Following a washout period, the same rats were re-dosed and tested in either a dim/dark box (DDB) test or an open field test (OFT) to evaluate anxiety in the absence of bright light. Cephalic allodynia, used as an indicator of headache-like pain, was assessed with von Frey measurements. RESULTS: CGRP-injected rats of both sexes spent significantly less time in the bright compartment of the LDB than controls. This avoidance was absent in the DDB test, and no CGRP-related effect was seen in the…
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