Increased Phosphorylation of Extracellular Signal-Regulated Kinase in Trigeminal Nociceptive Neurons Following Propofol Administration in Rats

Abstract

Although propofol (PRO) is widely used in clinic as a hypnotic agent, the underlying mechanisms of its action on pain pathways is still unknown. Sprague-Dawley rats were assigned to receive PRO or pentobarbital (PEN) and were divided into two groups as LIGHT and DEEP hypnotic levels based on the EEG analysis. Rats in each hypnotic level received capsaicin injection into the face and phosphorylated extracellular regulated-kinase (pERK) immunohistochemistry were performed in subnucleus caudalis (Vc) and upper cervical spinal cord. A large number of pERK-like immunoreactive (LI) cells was observed in the trigeminal spinal subnuclei interpolaris and caudalis transition zone (Vi/Vc), middle Vc and transition zone between Vc and upper cervical spinal cord (Vc/C2) in the rats with PEN or PRO administration following capsaicin injection into the whisker pad region. The number of pERK-LI cells in Vi/Vc, middle Vc and Vc/C2 was significantly larger in rats with PRO injection than those with PEN injection. The number of pERK-LI cells was increased following an increase in the dose of PRO but not in PEN. The pERK-LI cells were dominantly distributed in the Vi/Vc, middle Vc and Vc/C2 after the bolus injections of PRO. The expression of pERK-LI cells was depressed after the intravenous lidocaine application before PRO injection. The present findings suggested that PRO induced an enhancement of the activity of trigeminal nociceptive pathways through nociceptors innervating the venous structure, as indicated by a lidocaine-sensitive increase in pERK. This may explain deep pain around the injection regions during intravenous bolus injection of PRO.*To whom all correspondence should be addressed. Telephone number: +81 -3 -3219 -8112 Fax number: +81 -3 -3219 -8341 e-mail address: E-mail: iwata-k@dent.nihon-u.ac.jp. Perspective: The effect of propofol administration on ERK phosphorylation in the subregions of the spinal trigeminal complex and upper cervical spinal cord neurons were precisely analyzed in rats with PRO injection. A large number of pERK-LI cells was observed following intravenous PRO administration, suggesting an enhancement of trigeminal nociceptive activity and that PRO may produce pain through nociceptors innervating the venous structures during infusion. NIH Public AccessAuthor Manuscript J Pain. Author manuscript; available in PMC 2010 June 1.

Capsaicin Impairs Proliferation of Neural Progenitor Cells and Hippocampal Neurogenesis in Young Mice

“…However, several studies reported that capsaicin-induced apoptosis and pain responses in neurons are mediated by ERK activation (Gao & Ji, 2009;Shirakawa et al, 2008;Shoda et al, 2009). Data thus suggest that capsaicin may have cell-type-specific properties in proliferating cells and postmitotic neurons.…”

The Role Of Trigeminal Interpolaris-Caudalis Transition Zone In Persistent Orofacial Pain

“…While the caudal peak of neuronal activity varies rostrocaudally and mediolaterally in the Vc according to somatotopy, the rostral peak is consistently located at the obex or the trigeminal transition zone level (Strassman and Vos, 1993). Further, anesthetic alone induces Fos protein expression and increased phosphorylation of the extracellular signal-regulated kinase in the Vi/Vc transition zone (Imbe et al ., 1999; Shoda et al ., 2009). These findings suggest that neuronal activation in the ventral Vi/Vc transition zone lacks somatotopy, although there are selective primary afferent inputs to the Vi/Vc transition zone (Klineberg, 1971; Shigenaga et al ., 1988; Pozo and Cervero 1993; Zhou et al ., 1999; Hirata et al ., 1999; Imbe et al ., 1999; Wang et al ., 2006).…”

Involvement of Trigeminal Transition Zone and Laminated Subnucleus Caudalis in Masseter Muscle Hypersensitivity Associated with Tooth Inflammation

“…Extracellular signal-regulated protein kinase (ERK) is a member of mitogen-activated protein kinase family that can be activated by calcium influx within 10 min after noxious stimulation [11] . Phosphorylated ERK-immunoreactive (pERK-IR) cells are known to be distributed in Vc with somatotopic organization, and the number of pERK-IR cells increased in an intensity-dependent manner in the Vc [12] .…”