Abstract

BACKGROUND
Patients with complex regional pain syndrome have increased tryptase in the skin of the affected extremity indicating mast cell (MC) accumulation and degranulation, processes known to be mediated by substance P (SP). The dysregulation of SP release from primary afferent neurons is characteristic of complex regional pain syndrome. The authors hypothesized that SP acting through the neurokinin-1 receptor results in mast cell accumulation, degranulation, and nociceptive sensitization in a rat model of complex regional pain syndrome.
METHODS
Groups of 6-10 rats underwent tibia fracture and hind limb casting for 4 weeks, and the hind paw skin was harvested for histologic and immunohistochemical analysis. The effects of a selective neurokinin-1 receptor antagonist (LY303870) and of direct SP intraplantar injection were measured. Dermal MC degranulation induced by sciatic nerve stimulation and the effects of LY303870 on this process were investigated. Finally, the antinociceptive effects of acute and chronic treatment with a MC degranulator (48/80) were tested.
RESULTS
The authors observed that fracture caused MC accumulation, activation, and degranulation, which were inhibited by LY303870; the percentage of MCs in close proximity to peptidergic nerve fibers increased after fracture; electrical stimulation caused MC activation and degranulation, which was blocked by LY303870; intraplantar SP-induced MC degranulation and acute administration of 48/80 caused MC degranulation and enhanced postfracture nociception, but MC-depleted animals showed less sensitization.
CONCLUSIONS
These results indicate that facilitated peptidergic neuron-MC signaling after fracture can cause MC accumulation, activation, and degranulation in the injured limb, resulting in nociceptive sensitization.

Links

PMC Free PDF

Publisher Full Text

Authors

Li WW, Guo TZ, Liang DY, Sun Y, Kingery WS, Clark JD

Institution

Physical Medicine and Rehabilitation Service, Anesthesiology Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, California 94304, USA.

Source

Anesthesiology 116:4 2012 Apr pg 882-95

MeSH

Animals
Complex Regional Pain Syndromes
Disease Models, Animal
Indoles
Male
Mast Cells
Nociception
Pain Measurement
Piperidines
Rats
Rats, Sprague-Dawley
Receptors, Neurokinin-1
Substance P
Tibial Fractures

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22343473