Abstract:
AIMS:Investigate the involvement of the histaminergic projections from tuberomammillary nucleus (TMN) to the spinal cord in the modulation of nociception and peripheral edema in a model of monoarthritis. MAIN METHODS:Subacute monoarthritis was induced by an intraarticular injection of carrageenan followed by LPS 72 h later. Disability and joint edema were assessed at the 3rd hour after LPS and at every hour up to 6 h. KEY FINDINGS:Intrathecal administration of histamine potentiated joint incapacitation and edema, while the H1R antagonist cetirizine decreased both. The H3R agonist immepip decreased both incapacitation and edema, while the H3R antagonist thioperamide had the opposite effect. The microinjection of glutamate into the ventral TMN (vTMN) caused an increase of incapacitation and articular edema, whereas the blockade of this nucleus by cobalt chloride inhibited both parameters. Intrathecal administration of cetirizine prevented the increase of incapacitation and joint edema caused by glutamate microinjection into the vTMN. Similarly, an intrathecal injection of the NKCC1 cotransporter inhibitor bumetanide prevented the effects of glutamate microinjection into the vTMN, whereas coadministration of histamine with bumetanide only inhibited the potentiation of joint edema. A microinjection of orexin B into the vTMN potentiated incapacitation and joint edema, while coadministration of the OX1/2 receptor antagonist almorexant with orexin B did not. SIGNIFICANCE:These data support the notion that TMN participates in the modulation of a peripheral inflammatory process by means of histaminergic projections to the spinal cord, and the hypothalamus may trigger TMN activation by means of glutamate and orexin.
journal_name
Life Scijournal_title
Life sciencesauthors
Stein T,Tonussi CRdoi
10.1016/j.lfs.2020.118521subject
Has Abstractpub_date
2020-12-01 00:00:00pages
118521eissn
0024-3205issn
1879-0631pii
S0024-3205(20)31274-1journal_volume
262pub_type
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