Impairment of VGLUT2 but not VGLUT1 signaling reduces neuropathy-induced hypersensitivity.
Glutamate is the major excitatory neurotransmitter in the central nervous system with an important role in nociceptive processing. Storage of glutamate into vesicles is controlled by vesicular glutamate transporters (VGLUT). Null mutants for VGLUT1 and VGLUT2 were poorly viable, thus, pain-related behavior was presently compared between heterozygote VGLUT1 and VGLUT2 mice and their respective wild-type littermates using a test battery that included a variety of assays for thermal and mechanical acute nociception, and inflammatory and neuropathic pain syndromes. Behavioral analysis of VGLUT1 mutant mice did not show important behavioral changes in the pain conditions tested. Reduction of VGLUT2 also resulted in unaltered acute nociceptive and inflammatory-induced pain behavior. Interestingly, VGLUT2 heterozygote mice showed an attenuation or absence of some typical neuropathic pain features (e.g., absence of mechanical and cold allodynia after spared nerve injury). Chronic constriction injury in VGLUT2 heterozygote mice showed also reduced levels of cold allodynia, but had no impact on mechanical thresholds. Together, these data suggest that VGLUT2, but not VGLUT1, plays a role in neuropathy-induced allodynia and hypersensitivity, and might be a therapeutic target to prevent and/or treat neuropathic pain.
Leo
Sandra
S
Johnson and Johnson Pharmaceutical Research and Development, Janssen Pharmaceutica, Turnhoutseweg 30, B-2340 Beerse, Belgium. Sandra.Leo@psy.kuleuven.be
Moechars
Dieder
D
Callaerts-Vegh
Zsuzsanna
Z
D'Hooge
Rudi
R
Meert
Theo
T
D000818:Animals; D001259:Ataxia / Q000235:genetics / Q000503:physiopathology; D001522:Behavior, Animal / Q000502:physiology; D002351:Carrageenan; D003251:Constriction, Pathologic / Q000503:physiopathology; D005557:Formaldehyde; D006358:Hot Temperature; D006930:Hyperalgesia / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology; D007249:Inflammation / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010523:Peripheral Nervous System Diseases / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology; D010812:Physical Stimulation; D004856:Postural Balance / Q000502:physiology; D011930:Reaction Time / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013003:Somatosensory Cortex / Q000502:physiology; D020429:Tibial Neuropathy / Q000235:genetics / Q000503:physiopathology; D050598:Vesicular Glutamate Transport Protein 1 / Q000235:genetics / Q000502:physiology*; D050599:Vesicular Glutamate Transport Protein 2 / Q000235:genetics / Q000502:physiology*
C493477:Slc17a6 protein, mouse; C493465:Slc17a7 protein, mouse; D050598:Vesicular Glutamate Transport Protein 1; D050599:Vesicular Glutamate Transport Protein 2; D005557:Formaldehyde; D002351:Carrageenan