Cutaneous tactile allodynia associated with microvascular dysfunction in muscle
- Equal contributors
1 Department of Anesthesia, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec, H3G 1Y6, Canada
2 Alan Edwards Centre for Research on Pain, McGill University, 740 Dr. Penfield Ave, Montreal, Quebec, H3A 1A4, Canada
3 Department of Psychology, McGill University, 1205 Dr. Penfield Ave, Montreal, Quebec, H3A 1B1, Canada
4 Faculty of Dentistry, McGill University, 3640 University St, Montreal, Quebec, H3A 2B2, Canada
5 Department of Medical Informatics, Erasmus University Medical Centre, dr. Molewaterplein 50, 3015 GE Rotterdam, the Netherlands
6 Department of Neuroscience, Douglas Mental Health University Institute, 6875 LaSalle Boulevard, Verdun, Quebec, H4H 1R3, Canada
7 Department of Anesthesiology, Pain Treatment Centre, Erasmus University Medical Centre, S. Gravendijkwal 230, 3015 CE Rotterdam, the Netherlands
8 McGill University Hospital Centre Research Institute, 2155 Guy St, Montreal, Quebec, H3H 2R9, Canada
Molecular Pain 2008, 4:49 doi:10.1186/1744-8069-4-49Published: 28 October 2008
Cutaneous tactile allodynia, or painful hypersensitivity to mechanical stimulation of the skin, is typically associated with neuropathic pain, although also present in chronic pain patients who do not have evidence of nerve injury. We examine whether deep tissue microvascular dysfunction, a feature common in chronic non-neuropathic pain, contributes to allodynia.
Persistent cutaneous allodynia is produced in rats following a hind paw ischemia-reperfusion injury that induces microvascular dysfunction, including arterial vasospasms and capillary slow flow/no-reflow, in muscle. Microvascular dysfunction leads to persistent muscle ischemia, a reduction of intraepidermal nerve fibers, and allodynia correlated with muscle ischemia, but not with skin nerve loss. The affected hind paw muscle shows lipid peroxidation, an upregulation of nuclear factor kappa B, and enhanced pro-inflammatory cytokines, while allodynia is relieved by agents that inhibit these alterations. Allodynia is increased, along with hind paw muscle lactate, when these rats exercise, and is reduced by an acid sensing ion channel antagonist.
Our results demonstrate how microvascular dysfunction and ischemia in muscle can play a critical role in the development of cutaneous allodynia, and encourage the study of how these mechanisms contribute to chronic pain. We anticipate that focus on the pain mechanisms associated with microvascular dysfunction in muscle will provide new effective treatments for chronic pain patients with cutaneous tactile allodynia.