• Mol Pain · Jan 2016

    Consistent sex-dependent effects of PKMζ gene ablation and pharmacological inhibition on the maintenance of referred pain.

    • Hibatulnaseer Nasir, Hicham Mahboubi, Sandeep Gyawali, Stephanie Ding, Aiste Mickeviciute, RagavendranJ VaigundaJVAlan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada.Departmen... more t of Anesthesia, McGill University, Montreal, QC, Canada., André Laferrière, Ursula Stochaj, and Terence J Coderre. less
    • Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada.
    • Mol Pain. 2016 Jan 1; 12.

    BackgroundPersistently active PKMζ has been implicated in maintaining spinal nociceptive sensitization that underlies pain hypersensitivity. However, evidence for PKMζ in the maintenance of pain hypersensitivity comes exclusively from short-term studies in males using pharmacological agents of questionable selectivity. The present study examines the contribution of PKMζ to long-lasting allodynia associated with neuropathic, inflammatory, or referred visceral and muscle pain in males and females using pharmacological inhibition or genetic ablation.ResultsPharmacological inhibition or genetic ablation of PKMζ reduced mild formalin pain and slowly developing contralateral allodynia in nerve-injured rats, but not moderate formalin pain or ipsilateral allodynia in models of neuropathic and inflammatory pain. Pharmacological inhibition or genetic ablation of PKMζ also effectively reduced referred visceral and muscle pain in male, but not in female mice and rats.ConclusionWe show pharmacological inhibition and genetic ablation of PKMζ consistently attenuate long-lasting pain hypersensitivity. However, differential effects in models of referred versus inflammatory and neuropathic pain, and in males versus females, highlight the roles of afferent input-dependent masking and sex differences in the maintenance of pain hypersensitivity.© The Author(s) 2016.

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