Abstract
BackgroundMigraine is a complex neurological disorder that is characterized by throbbing head pain, increased sensitivity to light, sound, and touch, as well as nausea and fatigue. It is one of the most common and most disabling disorders globally but mechanisms causing migraine are poorly understood. While head pain is a typical feature of attacks, they also often present with cutaneous hypersensitivity in the rest of the body. In contrast, primary pain conditions in the lower parts of the body are less commonly associated with cephalic hypersensitivity. Previous studies indicate that application of stimuli to the meninges of rodents causes cutaneous facial as well as hindpaw hypersensitivity. In the present study, we asked whether widespread hypersensitivity is a unique feature of dural stimulation or whether body-wide responses occur similarly when the same stimulus is given in other locations.MethodsRats were given the same dose of IL-6 either via dural, intraplantar, subcutaneous, intramuscular, intracisternal, or intrathecal injection. Cutaneous facial and hindpaw allodynia was assessed using Von Frey following injection into each location.ResultsHindpaw allodynia was observed following dural and intraplantar injection of IL-6 in both males and females. Hindpaw allodynia was only observed in females following intracisternal and intrathecal IL-6 injections. In contrast, facial allodynia was only observed in either sex following dural and intracisternal injections, which would activate meningeal afferents and the trigeminal nucleus caudalis (TNC), respectively.ConclusionsHere we show that while stimulation of upper body regions with IL-6 including the meninges and brainstem can cause widespread hypersensitivity spreading to the paws, similar stimulation of the lower body does not cause the spread of hypersensitivity into the head. These data are consistent with the observations that whole body hypersensitivity is specific to conditions such as migraine where pain is present in the head and they may provide insight into co-morbid pain states associated with migraine.
Highlights
Migraine is a complex neurological disorder that is characterized by throbbing head pain, increased sensitivity to light, sound, and touch, as well as nausea and fatigue
While we have reported that dural IL-6 leads to facial allodynia in females [8], we did not test the ability of this stimulus to cause whole body allodynia in females
Given that cutaneous allodynia is more common in female migraineurs [25, 26] we aimed to test whether female rats would experience hindpaw allodynia to male rats
Summary
Migraine is a complex neurological disorder that is characterized by throbbing head pain, increased sensitivity to light, sound, and touch, as well as nausea and fatigue It is one of the most common and most disabling disorders globally but mechanisms causing migraine are poorly understood. Migraineurs often report increased sensory sensitivity and cutaneous allodynia in extracephalic regions during migraine attacks [4,5,6,7] This is in contrast to other pain conditions in the lower body which are not typically associated with hypersensitivity in the head. Numerous prior studies using rodent migraine models have shown a remarkably consistent finding that stimulation of the dura mater causes cutaneous hypersensitivity of both the facial skin as well as that of the hindpaw [8,9,10,11,12] These prior studies show that headache-inducing conditions lead to widespread hypersensitivity in rodents as in humans. The purpose of the present work was to test, using the same stimulus applied to multiple locations throughout the rat, whether dural stimulation is unique in its ability to cause body-wide hypersensitivity
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