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Trigeminal nerve injury‐induced thrombospondin‐4 up‐regulation contributes to orofacial neuropathic pain states in a rat model
Author(s) -
Li K.W.,
Kim DS.,
Zaucke F.,
Luo Z.D.
Publication year - 2014
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1002/j.1532-2149.2013.00396.x
Subject(s) - neuropathic pain , infraorbital nerve , orofacial pain , medicine , nerve injury , allodynia , trigeminal nerve , anesthesia , peripheral nerve injury , spinal cord , spinal cord injury , nociception , neuroscience , hyperalgesia , sciatic nerve , surgery , psychology , receptor , psychiatry
Background Injury to the trigeminal nerve often results in the development of chronic pain states including tactile allodynia, or hypersensitivity to light touch, in orofacial area, but its underlying mechanisms are poorly understood. Peripheral nerve injury has been shown to cause up‐regulation of thrombospondin‐4 ( TSP4 ) in dorsal spinal cord that correlates with neuropathic pain development. In this study, we examined whether injury‐induced TSP4 is critical in mediating orofacial pain development in a rat model of chronic constriction injury to the infraorbital nerve. Methods Orofacial sensitivity to mechanical stimulation was examined in a unilateral infraorbital nerve ligation rat model. The levels of TSP4 in trigeminal ganglia and associated spinal subnucleus caudalis and C1/C2 spinal cord ( Vc/C2 ) from injured rats were examined at time points correlating with the initiation and peak orofacial hypersensitivity. TSP4 antisense and mismatch oligodeoxynucleotides were intrathecally injected into injured rats to see if antisense oligodeoxynucleotide treatment could reverse injury‐induced TSP4 up‐regulation and orofacial behavioural hypersensitivity. Results Our data indicated that trigeminal nerve injury induced TSP4 up‐regulation in Vc/C2 at a time point correlated with orofacial tactile allodynia. In addition, intrathecal treatment with TSP4 antisense, but not mismatch, oligodeoxynucleotides blocked both injury‐induced TSP4 up‐regulation in Vc/C2 and behavioural hypersensitivity. Conclusions Our data support that infraorbital nerve injury leads to TSP4 up‐regulation in trigeminal spinal complex that contributes to orofacial neuropathic pain states. Blocking this pathway may provide an alternative approach in management of orofacial neuropathic pain states.