Indwelling Supradural Catheters for Induction of Facial Allodynia: Surgical Procedures, Application of Inflammatory Stimuli, and Behavioral Testing

Abstract

Migraine headaches are debilitatingly painful and poorly managed. Facial allodynia is often associated with migraine, and clinical evidence indicates that it is a critical point in migraine progression. That is, if the migraine can be treated prior to the onset of facial allodynia, the migraine can be halted using triptans, whereas if treatment is administered after facial allodynia has begun, the treatment is ineffective. The meninges and the immune cells therein have been implicated in migraine facial pain. Indeed, application of inflammatory mediators over the meninges has been used to study changes in pain responsive neurons in trigeminal complex, and changes in their receptive fields. Much of this research has been carried out in anesthetized rats, which limits the clinical application. Our indwelling supradural catheter model, in which inflammatory mediators can be administered to the meninges in awake and freely moving rats, allows for the assessment of behavioral changes shortly after injection. Following administration of inflammatory soup (histamine, serotonin, bradykinin, and prostaglandin E2) or the immunogenic HIV-1 coat protein gp120 results in reliable periorbital mechanical allodynia. This model provides an additional means to study the neurocircuitry and neuropharmacology of facial allodynia. Here, we describe detailed methods for the placement of the catheter, injection procedures, and assessment of facial allodynia.

Effects of diet-induced obesity on motivation and pain behavior in an operant assay

“…However, the study of head pain in rodents is challenging. Although some have successfully assessed mechanical allodynia in the trigeminal distribution in rats (Oshinsky and Gomonchareonsiri, 2007, Edelmayer et al, 2009, Liverman et al, 2009, Wieseler et al, 2012), very few studies have been published using mice (Krzyzanowska et al, 2011, Yasuda et al, 2012), underscoring the difficulty in translating traditional methods from rats to mice. The operant assay we used represents an objective, reproducible, automatized method to assess thermal nociception in the face of both rats and mice (Neubert et al, 2005, Neubert et al, 2008, Nolan et al, 2011b).…”

Animal models of migraine and experimental techniques used to examine trigeminal sensory processing

“…Response to mechanical stimulation using von Frey monofilament testing of the periorbital region in the awake behaving animal was therefore a critical evolution of the migraine pain model (see Behavior section). To permit behavioral testing in response to chemical dural stimulation, various models have been developed to allow for administration of substances in conscious behaving animals [66–69]. Repetitive inflammatory soup administration induces a chronic periorbital hypersensitivity to tactile stimuli that lasted for up to 3 weeks, suggestive of a model of chronic migraine [70].…”

Medication-overuse headache and opioid-induced hyperalgesia: A review of mechanisms, a neuroimmune hypothesis and a novel approach to treatment

“…Glial involvement in headache following opioid exposure has been evaluated pre-clinically using a rodent model of headache and morphine administration. In this study the authors were able to demonstrate that pre-exposure to an opioid results in facial allodynia, a surrogate for headache pain, during application of inflammatory “soup” to the dura in doses that fail to produce allodynia in opioid-naïve rats (131). When low-dose inflammatory soup was applied following morphine administration but prior to a dose of inflammatory soup able to reliably produce robust facial allodynia, no pain facilitation was observed, mirroring the clinical observation that MOH does not develop de novo in those without a pre-existing headache condition (131).…”

“…In this study the authors were able to demonstrate that pre-exposure to an opioid results in facial allodynia, a surrogate for headache pain, during application of inflammatory “soup” to the dura in doses that fail to produce allodynia in opioid-naïve rats (131). When low-dose inflammatory soup was applied following morphine administration but prior to a dose of inflammatory soup able to reliably produce robust facial allodynia, no pain facilitation was observed, mirroring the clinical observation that MOH does not develop de novo in those without a pre-existing headache condition (131). The exacerbation of head pain observed was attributed to opioid-induced glial activation as co-administration of the glial attenuator ibudilast with morphine was able to prevent facial allodynia (132).…”