An Experimental Model of Headache-Related Pain

Migraine patients often demonstrate cutaneous allodynia, defined as a hypersensitivity of the skin to touch or mechanical stimuli that are normally innocuous. The allodynia sometimes begins intracranially and spreads, via unknown mechanisms, to extracranial regions. The goal of the study was to develop and validate a model of cutaneous allodynia triggered by dural inflammation for this aspect of pain associated with headaches. Inflammatory mediators (IM) were applied to the dura of non-anesthetized rats via previously implanted cannulas and sensory thresholds of the face and hindpaws were characterized. IM elicited robust and time-related facial and hindpaw allodynia which peaked after approximately 3 h. These effects were reminiscent of cutaneous allodynia seen in patients with migraine or other primary headache conditions, and were reversed by agents used clinically in the treatment of migraine. Facial and hindpaw allodynia associated with dural stimulation is a useful surrogate of allodynia associated with primary headache including migraine likely reflecting the development of central sensitization and may be exploited mechanistically for the development of novel therapeutic strategies for headache pain.