The transient receptor potential ankyrin-1 mediates mechanical hyperalgesia induced by the activation of B1receptor in mice.
The kinin receptor B1and the transient receptor potential ankyrin 1 (TRPA1) work as initiators and gatekeepers of nociception and inflammation. This study reports that the nociceptive transmission induced by activation of B1receptor is dependent on TRPA1 ion channel. The mechanical hyperalgesia was induced by intrathecal (i.t.) injection of B1agonist des-Arginine9-bradykinin (DABK) or TRPA1 agonist cinnamaldehyde and was evaluated by the withdrawal response after von Frey Hair application in the hind paw. After behavioral experiments, lumbar spinal cord and dorsal root ganglia (DRG) were harvested to assess protein expression and mRNA by immunohistochemistry and real time-PCR, respectively. The pharmacological antagonism (HC030031) or the down-regulation of TRPA1 greatly inhibited the mechanical hyperalgesia induced by DABK. Intrathecal injection of DABK up regulated the ionized calcium binding adaptor molecule (Iba-1) in lumbar spinal cord (L5-L6); TRPA1 protein and mRNA in lumbar spinal cord; and B1receptor mRNA in both lumbar spinal cord and DRG. The knockdown of TRPA1 prevented microglia activation induced by DABK. Furthermore, the mechanical hyperalgesia induced by either DABK or by cinnamaldehyde was significantly reduced by inhibition of cyclooxygenase (COX), protein kinase C (PKC) or phospholipase C (PLC). In summary, this study revealed that TRPA1 positively modulates the mechanical hyperalgesia induced by B1receptor activation in the spinal cord and that the classical GPCR downstream molecules PLC, diacylglycerol (DAG), 3,4,5-inositide phosphate (IP3) and PKC are involved in the nociceptive transmission triggered by these two receptors.
Centro de Inovação e Ensaios Pré-clínicos (CIEnP), Cachoeira do Bom Jesus, Florianópolis, SC, Brazil.
Flavia Carla
FC
Meotti
Faculdade de Farmácia - Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil; Centro de Inovação e Ensaios Pré-clínicos (CIEnP), Cachoeira do Bom Jesus, Florianópolis, SC, Brazil.
Cláudia Pinto
CP
Figueiredo
Centro de Inovação e Ensaios Pré-clínicos (CIEnP), Cachoeira do Bom Jesus, Florianópolis, SC, Brazil.
Marianne
M
Manjavachi
Centro de Inovação e Ensaios Pré-clínicos (CIEnP), Cachoeira do Bom Jesus, Florianópolis, SC, Brazil. Electronic address: joao.calixto@cienp.org.br.
João B
JB
Calixto
D000818:Animals; D006930:Hyperalgesia / Q000503:physiopathology*; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D043783:Receptor, Bradykinin B1 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D012333:RNA, Messenger; D043783:Receptor, Bradykinin B1; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse
Kinin receptor B(1); Mechanical hyperalgesia; Nociceptive transmission; Spinal cord; TRPA1