Roles of HMGB1 in spread of pain sensitization of trigeminal neuropathic pain
10.3867/j.issn.1000-3002.2023.07.104
- Author:
Yu DU
1
,
2
;
Cenglin XU
;
Jie YU
;
MASAHIRO NISHIBORI
;
Zhong CHEN
;
Shihong ZHANG
Author Information
1. Department of Pharmacology and Department of Anes-thesiology of the Second Affiliated Hospital,Zhejiang Uni-versity School of Medicine,Hangzhou 310058,China
2. Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province,College of Pharmaceutical Sciences,Zhejiang Chinese Medical University,Hangzhou 310053,China
- Keywords:
trigeminal pain;
ventral posteromedial tha-lamic nucleus;
afferent remodeling;
HMGB1
- From:
Chinese Journal of Pharmacology and Toxicology
2023;37(7):523-524
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE Trigeminal pain is mostly uni-lateral orofacial,but pain sensitization often spreads to contralateral orofacial or distal body regions.Widespread trigeminal pain has more severe intensity,longer dura-tion,and wider distribution,accompanied by more serious comorbid emotional syndrome.Unfortunately,the first-line analgesics for neuropathic pain has limited effect on widespread pain along with unavoidable side effects.In-depth understanding of the pathogenesis of wide-spread trigeminal pain is urgently needed.METHODS Trigeminal pain was induced by partial transection of the infraorbital nerve(p-IONX)and evaluated by measur-ing nociceptive thresholds to mechanical or heat stimula-tion.Neuronal activity was evaluated by single-unit and patch clamp recordings.HMGB1 expression was mea-sured by immunohistochemistry.Antagonism of HMGB1 was achieved by injecting anti-HMGB1 monoclonal anti-body(mAb)intracerebrally or intraperitoneally.RESULTS P-IONX model induced not only orofacial algesia but also somatic algesia in hind paw.Spontaneous firing frequency of glutamatergic neurons in the ventral posteromedial tha-lamic nucleus(VPMGlu)as well as the amplitude and fre-quency of sEPSCs significantly increased after p-IONX.Moreover,calcium signal recording showed that VPMGlu became to be activated by the noxious mechanical stimu-lation given on the hind paw,suggesting that VPMGlu recruited somatic afferents after p-IONX.We further explored the upstream brain regions of VPMGlu by virus retrograde tracing.We found the afferents from the grac-ile nucleus/cuneate nucleus(Gr/Cu),which are involved in the conduction of somatic sensation,markedly increased.And chemogenetical inhibiting Gr/Cu-VPM circuit alleviated the widespread neuropathic pain.In addition,the expression of HMGB1 in the VPM was sig-nificantly increased after p-IONX.Local administration of anti-HMGB1 mAb in the VPM relieved widespread neuro-pathic pain in mice receiving p-IONX.CONCLUSION These results demonstrate that the remodeling of affer-ent neurons in VPM underlie the spreading of wide-spread trigeminal neuropathic pain.Highly expressed HMGB1 in VPM plays an important role in these patho-logical changes after nerve injury and systemic adminis-tration of anti-HMGB1 mAb concurrently relieves wide-spread pain.
