Somatostatin (SST) is a known neuromodulator of the central nervous system. The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc) receives many thinmyelinated Að-fiber and unmyelinated C primary afferent fibers and is involved in nociceptive processing. Many studies have demonstrated that SST plays a pivotal role in pain modulation in the spinal cord. However, little is yet known about the direct effects of SST on the SG neurons of the Vc in adult mice. In our present study, we investigated the direct membrane effects of SST and a type 2 SST receptor agonist, seglitide (SEG), on the SG neurons of the Vc using a gramicidin-perforated current clamp in adult mice. The majority (53%, n = 27/51) of the adult SG neurons were hyperpolarized by SST (300 nM) but no differences were found in the hyperpolarization response rate between males and females. When SST was applied successively, the second response was smaller (76±9.5%, n=19), suggesting that SST receptors are desensitized by repeated application. SST-induced hyperpolarization was also maintained under conditions where presynaptic events were blocked (75±1.0%, n=5), suggesting that this neuromodulator exerts direct effects upon postsynaptic SG neurons. SEG was further found to induce membrane hyperpolarization of the SG neurons of the Vc. These results collectively demonstrate that SST inhibits the SG neuronal activities of the Vc in adult mice with no gender bias, and that these effects are mediated via a type 2 SST receptor, suggesting that this is a potential target for orofacial pain modulation.

Bicuculline is one of the most commonly used GABAд eceptor antagonists in electrophysiological research. Because of its poor water solubility, bicuculline quaternary ammonium salts such as bicuculline methiodide (BMI) and bicuculline methbromide are preferred. However, a number of studies have shown that BMI has non-GABAд eceptor-mediated effects. The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc) is implicated in the processing of nociceptive signaling. In this study, we investigated whether BMI has non-GABA receptor-mediated activity in Vc SG neurons using a whole cell patch clamp technique. SG neurons were depolarized by application of BMI (20M) using a high Cℓ⁻ipette solution. GABA ( 30-100μM) also induced membrane depolarization of SG neuron. Although BMI is known to be a GABAд receptor antagonist, GABA-induced membrane depolarization was enhanced by co-application with BMI. However, free base bicuculline (fBIC) and picrotoxin (PTX), a GABAд and GABAс receptor antagonist, blocked the GABA-induced response. Furthermore, BMI-induced membrane depolarization persisted in the presence of PTX or an antagonist cocktail consisting of tetrodotoxin (Nα+ nnel blocker),AP-5 (NMDA receptor antagonist), CNQX (non-NMDA receptor antagonist), and strychnine (glycine receptor antagonist). Thus BMI induces membrane depolarization by directly acting on postsynaptic Vc SG neurons in a manner which is independent of GABAд receptors. These results suggest that other unknown mechanisms may be involved in BMI-induced membrane depolarization.

까le orofacial pain is one of the most common types of acute or chronic pain, and many forms of orofacial pain have an inflammatory component. The aim of this study was to develop a behavioral model of orofacial pain associated with chronic int1ammation in rats. 까le int1ammatory agent, CFA suspended in an oil/saline (1 :1) emulsion (50 씨) was injected into the vibrissal pad of adult male rats. A s따피ar application of saline was served as control. Spontaneous and mechanically evoked behaviours were monitored daily in awake rats before and up to 6 weeks after injection. As for the spontaneous behaviour, total time rat spent in face gr∞ming was counted. For the measurement of mechanically evoked behaviour, the threshold and frequency of head withdrawal response (HWR) were determined at the vibrissal pad with the use of von Frey nylon monofilaments. CFA injection did not produce any significant changes in face gr∞ming， but produced a s핑nificant reduction in HWR threshold and a s핑nificant increase in HWR frequency to mechanical stimulation of the vibrissal pad on the ipsilateral side for approximately 4-6 weeks. Saline injection into the vibrissal pad did not produce any significant changes in spontaneous and mechanically evoked behaviours. These results indicate that the injection of CFA into orofacial cutaneous tissues can induce persistent behavioral allodynia and hyperalgesia, and easily quantified behavioral model will provide a better understanding of mechanisms and control of orofacial chronic pain conditions associated with int1ammation.