Sciatica Research Today is a free monthly online journal that collates and summarizes the latest research about Sciatica, including details on treatment, prevention, medication.

A role for G protein-coupled receptor kinase 2 in mechanical allodynia.

Kleibeuker W, Ledeboer A, Eijkelkamp N, Watkins LR, Maier SF, Zijlstra J, Heijnen CJ, Kavelaars A

University Medical Center Utrecht, Laboratory of Psychoneuroimmunology, KC03.068.0, Lundlaan 6, 3584 EA, Utrecht, The Netherlands.

Inflammation and nerve injury can both induce mechanical allodynia via mechanisms involving the production of pro-inflammatory cytokines and increased neuronal activity. Many neurotransmitters involved in pain signal via G protein-coupled receptors (GPCRs). GPCR kinase (GRK)2 is a member of the GRK family that regulates agonist-induced desensitization and signalling of GPCRs. Low intracellular GRK2 levels are associated with increased receptor signalling. The aim of this study was to investigate whether mechanical allodynia is associated with decreased spinal cord GRK2 expression and whether reduced GRK2 increases inflammation-induced mechanical allodynia. Mechanical allodynia was induced in rats by chronic constriction injury of the sciatic nerve. After 2 weeks, neuronal GRK2 expression was decreased bilaterally in the superficial layers of the lumbar spinal cord dorsal horn. Moreover, interleukin-1beta significantly reduced GRK2 expression ex vivo in spinal cord slices. To investigate whether reduced GRK2 potentiates inflammation-induced mechanical allodynia, we used GRK2(+/-) animals expressing decreased GRK2. At baseline, the threshold for mechanical stimulation did not differ between GRK2(+/-) and wild-type mice. However, GRK2(+/-) animals were more sensitive to mechanical stimulation than wild-type animals after intraplantar lambda-carrageenan injection. We propose cytokine-induced down-regulation of spinal cord neuronal GRK2 expression as a novel mechanism that contributes to increased neuronal signalling in mechanical allodynia.

Published 16 April 2007 in Eur J Neurosci, 25(6): 1696-704.
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