Elsevier

Neuroscience

Volume 133, Issue 3, 2005, Pages 739-747
Neuroscience

Molecular neuroscience
Elimination of neurokinin-1 receptor neurons in caudal nucleus reverses the effects of systemic bicuculline on c-Fos expression in rat trigeminal sensory nucleus: I. High intensity electrical stimulation of the trigeminal ganglion

https://doi.org/10.1016/j.neuroscience.2005.03.021Get rights and content

Abstract

Although neurokinin-1 receptor (NK-1)-bearing neurons are distributed in lamina I of the trigeminal caudal nucleus (Vc) and constitute major projection neurons, little is known about their fundamental role(s) in nociceptive processing. This study examines the effect of intra cisterna magna injection of substance P (SP) conjugated to saporin (SP-Sap; 5μM, 5μl) [with/without systemic administration of bicuculline] on c-Fos expression in the trigeminal sensory nucleus (TSN) induced 2 h after 10 min repetitive electrical stimulation of the trigeminal ganglion (TG) at high intensity (1.0mA, 5Hz, 5 ms) in the urethane-anesthetized rat. In the SP-Sap-treated rats, the numbers of NK-1-immunopositive neurons in laminae I and III of the Vc decreased compared with rats similarly pretreated with saline (Sal; 5μl) or blank-saporin (Bl-Sap; 5μM, 5μl). In Sal- or Bl-Sap-treated controls, high intensity stimulation induced c-Fos expression in neurons throughout the full extent of ipsilateral superficial layers of the Vc (VcI/II), magnocellular zone of the Vc (VcIII/IV) and the dorsal or dorsomedial subdivisions of the rostral TSN above the obex (trigeminal principal, oral (Vo) and interpolar nuclei). Preadministration of bicuculline (2mg/kg, i.p.) decreased the numbers of c-Fos-immunopositive neurons in the VcI/II, VcIII/IV and Vo in Sal- or Bl-Sap-treated controls. In contrast, high intensity stimulation induced less c-Fos-immunopositive neurons in the VcI/II and Vo of rats treated with SP-Sap compared with those in Sal- or Bl-Sap-treated controls. In SP-Sap-treated rats preadministered with bicuculline, the numbers of c-Fos-immunopositive neurons in the VcI/II and Vo were increased compared with the SP-Sap-treated rats preadministered with Sal.

These results suggest that NK-1-immunopositive neurons in laminae I and III of Vc play a pivotal role in the nociceptive specific processing in the TSN through GABAA receptors.

Section snippets

Surgical operation

Experiments were conducted on 24 male Sprague-Dawley rats weighing 180–200g (Keari Co. Ltd, Osaka, Japan). Under anesthesia with Na-pentobarbital (50mg/kg i.p.), the animal was fixed to a stereotaxic apparatus and 5μl of 5μM SP-Sap (Advanced Targeting Systems, San Diego, CA, USA), non-conjugated (blank) saporin (Bl-Sap; Advanced Targeting Systems) or physiological saline (Sal) was injected into the cerebellomedullary cistern (cisterna magna) through posterior atlanto-occipital membrane. Two to

Effects of SP-Sap treatment on the immunoreactivity for NK-1

In Sal- and Bl-Sap-treated controls, immunoreactivity for NK-1 was recognized mostly in lamina I, and modestly in superficial lamina III of the Vc (Fig. 1). There was no labeling in the rostral TSN above the obex. The labeled neurons in lamina I extended tangential dendrites (Fig. 1) and made a relatively dense network in lamina I. In lamina III, smaller numbers of labeled neurons demonstrated several superficially oriented dendrites extending to lamina I. In Sal- and Bl-Sap-treated controls,

Technical consideration

The stimulation intensity-specific expression of c-Fos in the TSN has been precisely reported for two different intensities of electrical stimulation (Takemura et al 2000a, Takemura et al 2000b). The lower stimulus intensity (0.1mA) causes an excitation of A-fibers, but not C-fibers, while the higher stimulus (1.0mA) stimulates larger and at least some smaller caliber afferents (C-fibers) (Woolf and Wall, 1982). These findings were further supported by the studies of C-fiber components and

Acknowledgments

We thank D. M. Donovan for critical revision of the manuscript. This work was supported by a Grant-in-Aid for Scientific Research© from the Ministry of Education, Science/Sports and Culture of Japan (15591929).

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