A new animal model of headache: Ongoing pain vs stimulus-evoked hypersensitivity.

The field of basic pain research has had an ongoing need to develop better ways of assessing pain in animals, especially ‘‘spontaneous’’ or ongoing pain as opposed to tactile or thermal hypersensitivity (1–7). It has been argued that the lack of adequate behavioral assays for spontaneous pain is a key factor in the failure to develop new drugs for pain treatment, in spite of enormous advances in the understanding of basic mechanisms and the identification of molecular targets. The headache field in particular for many years suffered from the severe limitation of having no behavioral assay whatsoever. One exception was the finding of Malick et al. of a moderate decrease in feeding behavior over a six-hour period following chemical stimulation of the dura in awake rats (8). However, this finding was not pursued further as a behavioral assay, in part because of the relatively long observation time required. A major breakthrough for basic headache research came when Oshinsky and Gomonchareonsiri showed that chemical stimulation of the dura induced facial allodynia in awake rats, providing for the first time an acutely measureable behavioral correlate, albeit indirect, of ‘‘headache’’ in animals (9). However, the problem still remained of finding a behavioral correlate of ongoing or ‘‘spontaneous’’ headache pain, as opposed to the allodynia that can sometimes be an accompaniment to headache (10). This issue of Cephalalgia reports a finding that represents a further breakthrough for the study of headache: a new observation of a change in ‘‘spontaneous’’/ ongoing behavior following chemical stimulation of the dura in chronically prepared awake rats (11). This observation was made possible by exceptionally careful surgical implantation of the extradural cannula and acclimation of the rats to the observation environment, and second-by-second video analysis of ongoing behavior over a 45-minute observation period, made during the awake period of the animal’s circadian cycle. The core finding is a suppression of the exploratory behavior that normally occurs in control animals when placed into the observation chamber, and a concomitant increase in the amount of ‘‘resting’ behavior or quiet wakefulness. This observation might not in itself sound very remarkable. However, it is potentially of great significance as an example of the more general phenomenon of the suppression of an innate behavior/locomotor activity by pain. Such suppression is now being recognized as a new, powerful approach for assessing ‘‘spontaneous’’/ongoing pain, which has been put forth by Andrews and others who are at the forefront of developing new methods for the study of pain behavior in animals (6,7,12–15). This observation of a suppression of exploratory behavior has further significance in view of the long-standing idea that visceral pain is associated with a distinct response pattern, consisting of behavioral as well as autonomic quiescence and withdrawal, in contrast to the arousal and escape behavior evoked by superficial pain (16–19). Future studies could test the hypothesis that this suppression of exploratory behavior or other innate behaviors is greater following stimulation of deep rather than superficial tissues. This finding of Melo-Carillo and Lopez-Avila is in a sense more direct than that of Oshinsky and Gomonchareonsiri in that it is potentially a behavioral correlate of the headache itself, not merely the allodynia that can sometimes accompany headache. It may also prove to be a more sensitive assay, in that allodynia is present only in a subset of migraine attacks, whereas headache pain is (by definition) present in all attacks. The dural stimulus also induced a brief initial period of ipsilateral facial ‘‘grooming’’ or rubbing that