We compared mechanical pain thresholds in various orofacial areas. Twelve subjects (6 males, 6 females) aged 28 to 64 years participated in this study. They were seated in a supine position on a dental chair during measurement. The pain thresholds were measured at 38 sites in oral region, 7 sites in facial region, and 4 sites in the hand using an electronic von Frey instrument. The subjects were instructed to lift their left hands when they started to feel pain. The pain thresholds as the subjective sensation intensity were calculated on the basis of the Weber-Fechner law. The threshold values in 4 areas were as follows; red margin of the lip < oral mucosa < facial skin < skin of the hand (Bonferroni, p<0.05) and those in 9 oral areas were; frenum ≈ floor of mouth < red margin of the lip ≈ free gingiva ≈ tongue < lip mucosa < hard palate ≈ attached gingiva < Kiesow zone (Bonferroni, p<0.05). It is suggested that the mechanical pain thresholds in orofacial areas might be influenced by the density of free nerve endings,the degree of keratinization, and tissue thickness.

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   The last decade has seen the development of a particular interest in the role of purines in nociception. The ability of adenosine 5'-triphosphate (ATP) and adenosine to alter nociceptive transmission at peripheral and central sites has been recognized. The recent discovery of P2X receptors (ion channels gated by ATP) has led to the exploration of the sources of ATP involved in initiating different types of nociception. In addition, adenosine receptors in the spinal cord have generated great interest in the development of its agonists as potential analgesic drugs. Although each role of P2X and adenosine receptors in nociceptive transmission has been examined in detail, the interaction of their receptors has never been studied. In this study, we demonstrated that extracellular ATP induces a biphasic effect such as facilitation followed by inhibition of glutamatergic excitatory synaptic transmission in dorsal horn neurons of spinal cord slice preparations by use of patch-clamp recordings. The application of ATP made an initial facilitation of glutamate release via presynaptic P2X receptors, which lasted for only a short period. ATP was rapidly metabolized to adenosine which produced an inhibition of glutamate release onto dorsal horn neurons by activating adenosine receptors for a relatively longer period. Our results indicate that extracellular ATP exerts multiple influences on nociceptive transmission in the spinal cord.

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   The mechanisms of neuropathic pain following peripheral nerve injury have not been fully understood. Although it has recently reported that nerve growth factor (NGF) is possibly involved in regeneration of injured peripheral sensory neurons, there are only few evidences to confirm it in neuropathic pain. Therefore, we characterized the role of NGF in neuropathic pain after nerve injury by different action of treatments.
   Sprague-Dawley rats were subjected and the left sciatic nerve was loosely ligated (CCI model). To quantify the pain sensation the paw withdrawal latency (PWL) against thermal stimulation was periodically measured after CCI. Either day 5 or 14, the rats were subjected for microdialysis and perfused fixation for immunohistochemistry (c-fos). The modulatory effect of anti-NGF either with N-type Ca²⁺ channels blocker (ONO-2921) or magnetic field stimulation (MF) was considered.
   The PWL were increased with time from day 3 to day 14 after CCI. On day 5 to 14, the c-fos positive cells at Rexed 1-2 and 5-6 were seen accompanied with slight damage of Rexed 3-4 neurons (HE). 4-methyl catechol, as an inducer of NGF, attenuated neuropathic pain and this effect was moderately antagonized by anti-NGF. These behavioral and cell functional changes were significantly attenuated by ONO-2921 or MF treatments. However, the attenuating effect of MF was antagonized by anti-NGF while effects of ONO-2921 did not affect any.
   It is concluded that the neuropathic pain may result in excessive spinal glutamate release followed by an early gene expression at input region of c-fiber as “neuronal plasticity”. Further more, we suggest that insufficient of NGF may possibly be developing neuropathic pain and that magnetic field stimulation has beneficial effect through mechanisms by acceleration of neuronal regeneration induced by NGF. However, beneficial effect of N-type Ca²⁺ channels blocker may not involved by synthesis of NGF.

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   Introduction: µ-opioid receptor (MOR) internalization is caused by (DAMGO) and etorphine, but not by morphine in vitro and in vivo. MOR internalization caused by fentanyl is demonstrated only in vitro. The relationship between MOR internalization and analgesic effect caused by fentanyl has not been studied. In addition, the role of MOR internalization caused by opioid agonists in the analgesic effect in vivo has not been well established. In the present study, therefore, we examined whether fentanyl causes MOR internalization in vivo or not and also studied the relationship between MOR internalization and analgesic effect of opioid agonists.
   Methods: The protocol was approved by our animal research and use committee. Male Sprague-Dawley rats weighing 300–330 g were implanted with intrathecal catheters at the level of L4–5. Tail flick test was performed at 30 min after intrathecal administration of morphine, DAMGO, fentanyl, or saline. Immediately after the test, rats were perfused and the spinal cord was removed. MOR distribution was assessed by immunohistochemical staining of MOR in the dorsal horn neurons.
   Results: The opioid agonists exerted analgesic effect assessed by tail flick test at 30 min after injection. In morphine treated rats, no MOR internalization was observed in the laminae I and II neurons of the spinal cord, as was seen with saline. DAMGO caused MOR internalization in almost all of the neurons expressing MOR. Though fentanyl also produced internalization in the laminae I and II neurons, the internalization was observed in approximately half of the neurons expressing MOR, and the distribution of internalized MOR was different from that induced by DAMGO.
   Conclusion: Intrathecally administered fentanyl caused MOR internalization in the rat spinal dorsal horn neurons. MOR distribution showed different patterns depending on opioid agonists used. These results suggest that the MOR internalization does not seem to be involved in analgesic effect produced by opioid agonist.

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   In both the spared nerve injury (SNI) and spinal nerve ligation (SNL) rat peripheral neuropathic pain models, intrathecal injection of µ opioid receptor (MOR) agonist DAMGO fails to produce analgesia. Inhibition of primary afferent-evoked ERK (extracellular signal-regulated kinase) MAP kinase activation by DAMGO are suppressed following nerve injury. The normal presynaptic inhibitory effect of DAMGO on both primary afferent-evoked excitatory postsynaptic currents (EPSCs) and miniature EPSCs in superficial dorsal horn neurons is substantially reduced following SNI and SNL. The two nerve injury models also reduce the postsynaptic potassium channel opening action of DAMGO on lamina II spinal cord neurons. Diminished spinal opioid analgesia in neuropathic pain may reflect reduced activation of MOR on both injured primary afferent central terminals and the second order neurons they innervate.

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   We have reported that polymodal nociceptors are abundant in the temporomandibular joint (TMJ) region and that a lowered threshold of polymodal nociceptors is involved in TMJ pain (Takeuchi et al., 2001, 2003). In this study, we compared the effects of steroidal and non-steroidal anti-inflammatory drugs (SAID and NSAID, respectively) on the responses of C-Polymodal units, using an in vitro TMJ-nerve preparation. Male Wistar albino rats weighing about 250 - 350 g were used. Recordings were obtained from C-Polymodal units identified by its conduction velocity (below 2.0 m/s) and responsiveness to mechanical, thermal and chemical stimuli. Nociceptive responses were induced by topical administration of bradykinin (BK) to the TMJ area, while single unit activities were recorded from auricular-temporal nerve filaments by a tungsten microelectrode. In addition, nociceptive threshold was measured by von Frey hair stimulation during drug application. The frequency of the BK-induced unit activity and the mechanical nociceptive threshold were recorded before and after application of SAID (dexamethasone), NSAID (flurbiprofen), or physiological saline (control group). Dexamethasone and flurbiprofen significantly decreased the BK-induced nociceptive responses. The nociceptive threshold increased after application of anti-inflammatory drugs, indicating that bradykinin-induced mechanical sensitization was well inhibited by SAID and NSAID. Effect of dexamethasone was expressed immediately after its application, while that of flurbiprofen was expressed after a period of latency. These results show that different antiinflammatory drugs have different anti-nociceptive properties and that the adequate analgesic drug should be applied in the clinical field according to the type of TMJ pain.

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