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Controlling the activation of the B v8/prokineticin system reduces neuroinflammation and abolishes thermal and tactile hyperalgesia in neuropathic animals
Author(s) -
Maftei D,
Marconi V,
Florenzano F,
Giancotti L A,
Castelli M,
Moretti S,
Borsani E,
Rodella L F,
Balboni G,
Luongo L,
Maione S,
Sacerdote P,
Negri L,
Lattanzi R
Publication year - 2014
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12793
Subject(s) - neuroinflammation , neuropathic pain , hyperalgesia , medicine , nociceptor , allodynia , sciatic nerve , spinal cord , proinflammatory cytokine , pharmacology , astrocyte , nociception , anesthesia , central nervous system , receptor , endocrinology , inflammation , psychiatry
Background and Purpose Chemokines are involved in neuroinflammation and contribute to chronic pain processing. The new chemokine prokineticin 2 ( PROK2 ) and its receptors ( PKR 1 and PKR 2 ) have a role in inflammatory pain and immunomodulation. In the present study, we investigated the involvement of PROK2 and its receptors in neuropathic pain. Experimental Approach Effects of single, intrathecal, perineural and s.c. injections of the PKR antagonist PC1 , or of 1 week s.c. treatment, on thermal hyperalgesia and tactile allodynia was evaluated in mice with chronic constriction of the sciatic nerve ( CCI ). Expression and localization of PROK2 and of its receptors at peripheral and central level was evaluated 10 days after CCI , following treatment for 1 week with saline or PC1. IL ‐1β and IL ‐10 levels, along with glia activation, were evaluated. Key Results Subcutaneous, intrathecal and perineural PC1 acutely abolished the CCI ‐induced hyperalgesia and allodynia. At 10 days after CCI, PROK2 and its receptor PKR 2 were up‐regulated in nociceptors, in S chwann cells and in activated astrocytes of the spinal cord. Therapeutic treatment with PC1 (s.c., 1 week) alleviated established thermal hyperalgesia and allodynia, reduced the injury‐induced overexpression of PROK2 , significantly blunted nerve injury‐induced microgliosis and astrocyte activation in the spinal cord and restored the physiological levels of proinflammatory and anti‐inflammatory cytokines in periphery and in spinal cord. Conclusion and Implications The prokineticin system contributes to pain modulation via neuron–glia interaction. Sustained inhibition of the prokineticin system, at peripheral or central levels, blocked both pain symptoms and some events underlying disease progression.