Chemokine network in the nervous system: a new target for pain relief.
Physical insults including but not limited to nerve damage, inflammation, visceral pathologies and cancer generate long lasting pain commonly referred as chronic pain. Recently, members of the chemokine family and their receptors emerged as key modulators in nociceptive influx transmission in neuropathic and inflammatory chronic pain models. To this day, rodents defective in specific chemokine receptors have provided evidence of the implication of chemokine in pain sensitivity. In addition, up-regulation of chemokines and their receptors at multiple levels in the central nervous (CNS) and peripheral (PNS) systems is associated in the development of chronic pain. Indeed, we point out the fact that chemokines are synthesized and released by both neuronal and non-neuronal cells and act as neuromodulators. Even if their functional roles in the CNS remain largely unknown, chemokines participate in the glial activation and modulation of neuronal excitability as well as neurotransmitter release. This review focuses on three chemokines (i.e. CCL2, CXCL12, CX3CL1) recently identified as important mediators of the initiation and maintenance of pain hypersensitivity, thus broadening the panel of new strategies for the management of chronic pain.
Gosselin
R D
RD
Unités mixtes 732 & 713 INSERM, Université P et M Curie-Paris 06, Hôpital Saint-Antoine et Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Dansereau
M A
MA
Pohl
M
M
Kitabgi
P
P
Beaudet
N
N
Sarret
P
P
Mélik Parsadaniantz
S
S
D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D018925:Chemokines / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D015394:Molecular Structure; D009424:Nervous System Physiological Phenomena / Q000187:drug effects / Q000502:physiology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology*; D018121:Receptors, Cytokine / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D000700:Analgesics; D018925:Chemokines; D018121:Receptors, Cytokine