The aim of present study is to clarify neuronal mechanisms of an inhibition of swallowing reflex following capsaicin injection into the whisker pad skin or lingual muscle in anesthetized rats.　We analyzed the number of swallows induced by topical administration of 0.1 ml of water to the pharyngeal mucosa following capsaicin injection into the whisker pad skin or lingual muscle. The phosphorylated extracellular signal-regulated kinase (pERK) immunohistochemistry in the medulla and upper cervical spinal cord was also carried out in 10 mM capsaicin-treated rats.We also studied the effect of MAP kinase (MEK)1/2 inhibitor, PD98059, on pERK expression and swallowing reflex following 10 mM capsaicin injection into the whisker pad skin or lingual muscle.
   The number of swallows decreased in dose dependent manner following capsaicin injection into the whisker pad skin or lingual muscle. The number of pERK-like immunoreactive (pERK-LI) cells in the nucleus tractus solitarii (NTS), trigeminal spinal subnucleus caudalis (Vc) and paratrigeminal nucleus (Pa5) was significantly larger in the rats with capsaicin treatment compared to vehicle-treated rats. After intrathecal (i.t.) injection of PD98059 in the rats with capsaicin treatment, the number of pERK-LI cells was significantly depressed compared to vehicle-treated rats.Swallowing reflex was significantly enhanced in PD98059-treated rats compared to vehicle-treated rats.
   These findings suggest that the ERK phosphorylation in NTS and Pa5 neurons is involved in modulation of swallowing reflex following noxious stimulation of the orofacial regions.

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   Objective. Based on the results of a drug-challenge test with ketamine, we applied low-dose ketamine drip infusion (LDKI) therapy combined with dual-lead spinal cord stimulation therapy (Dual-SCS) for the treatment of various kinds of neuropathic pain. We report about benefits of this combined therapy.
   Methods. In the drug-challenge test with ketamine, 5 mg of ketamine hydrochloride (i.v.) was given every 5 min up to 25 mg. Ketamine hydrochloride (0.33 mg/kg) added to 100 ml of saline was administered intravenously by 1-hour drip infusion every 2 weeks for LDKI therapy. Combined with this LDKI therapy, Dual-lead SCS therapy was applied for the treatment of various kinds of neuropathic pain.
   Results. Comparing with single-lead SCS, Dual-lead SCS had obvious advantages to evoke paresthesia restricted only over the painful area. LDKI therapy directly and markedly reduced the intractable pain from 1 hour to 3 days, and also increased the effects of Dual-lead SCS for CRPS, failed-back syndrome, post-stroke pain, and phantom limb pain.
   Conclusion. Dual-lead SCS combined with LDKI therapy is useful for the treatment of various kinds of neuropathic pain. Even if the direct effect of ketamine is transient, effects that provide release from central sensitization and the wind-up phenomenon may be important to increase the effects of Dual-lead SCS.

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Introduction: Previous reports have investigated the relationship between pain and suicide. On the other hand, we have treated some patients that complain suicidal ideation and attempt suicide, in spite of unbearable low back pain is removed. Therefore, the present study investigated suicide-related symptoms (suicidal ideation or suicide attempt) after removal of low back pain by comparing patients with depression and low back pain with patients with depression and headache.
Methods: The subjects were inpatients with depression who were treated at Jichi Medical University Hospital from April 1997 to March 2006. From among 138 patients who complained of pain for over one week, patients with either headache or low back pain were selected and divided into two groups, according to their region of pain. The “low back pain" group (n=22) consisted of patients who only complained of low back pain, while the “headache" group (n=26) consisted of patients who only complained of headache. Subsequently, these groups were statistically analyzed by comparing both with regard to hypochondriacal symptoms, suicide-related symptoms, and suicide-related symptoms after removal of pain.
Results: The “low back pain" group had significantly more hypochondriacal symptoms and suicide-related symptoms after removal of pain than the “ headache" group. With regard to suicide-related symptoms, no significant difference was observed.
Conclusion: These results suggest that the hyochondriacal complaint of low back pain is a manic element that mingles with the depressive phase. When low back pain is removed, patients can no longer complain of low back pain, thus the manic element of the depressive phase is lost. Consequently, it is thought that depression worsens and suicide-related symptoms appear.
In the treatment of low back pain among patients with depression, it is important to remain aware that some patients may attempt suicide after low back pain is removed.

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   We have previously reported the efficacy of navigation-guided 5-Hz repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex in relief of intractable neuropathic pain. The objective of this study was to assess changes of cortical excitability induced by rTMS which might give an insight to the mechanism of pain relief with rTMS. In 14 patients with neuropathic pain in a hand and five healthy controls, the cortical excitability and visual analogue scale (VAS) were evaluated before and after 5Hz-rTMS of the primary motor cortex corresponding to the painful hand. Resting motor threshold, amplitude of motor evoked potential, cortical silent period, intracortical inhibition and intracortical facilitation (ICF) were measured as parameters of cortical excitability with single- or paired-pulse TMS method. The patients who showed ≥ 30% pain reduction in VAS after rTMS were classified as “good responders", the others were as “poor responders". Five of 14 patients were good responders,in whom ICF was significantly lower than that in controls at baseline (p=0.039). ICF increase induced by rTMS was significantly higher in good responders than in poor responders (p=0.046). There were no significant differences and changes in the other parameters. Our findings suggested that restoration of the abnormal cortical excitability was one of the mechanism underling the pain relief with rTMS in neuropathic pain.

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   The loss of a limb leads to sensorimotor modifications. Patients often vividly experience that the missing limb is still present (phantom limb), and that it can be moved at will. Transcranial magnetic stimulation (TMS) to the primary motor cortex (M1) of such amputees induces the sensation of movement of the phantom limb.
   In this study, TMS was applied for functional mapping of the motor cortex in patients with deafferentation pain. We studied 7 patients with intractable deafferentation pain (phantom limb: 3, brachial plexus avulsion: 4) and 2 patients with spinal cord injury without pain. Navigation-guided TMS stimulated their cortices around the primary motor area. The motor evoked potential (MEP) and the TMS-induced sensation reported by the patients were recorded. In all the patients, TMS induced some sensation of their amputated or paralyzed limbs.In the patients with phantom limb pain, the sensation was evoked by TMS to both the contralateral and ipsilateral cerebral hemispheres.
   Conversely, in the patients without pain, TMS to the ipsilateral hemisphere did not evoke sensations of their paralyzed arm.In conclusion, TMS demonstrated marked cortical reorganization across the cerebral hemispheres in those patients with phantom limb pain.

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   Clinically, it is known that the incidence of chronic pain is much lower in children than in adults. The low-incidence may disclose some important factors to develop chronic pain in the adulthood. In this study, we examined whether the treatment to young rats would induce the chronic pain behavior, using the myopathic chronic pain animal model we previously developed.
   Lipopolysaccharide (LPS: 2 µg/kg) and hypertonic saline (6%) were injected into the uni-lateral gastrocnemius muscle of rats of postnatal three weeks (young) and nine weeks (adult). The treatment to adult rats produced long-persisting pain behaviors as the previous reported, on the contrary, the treatment to young rats did not develop chronic pain behaviors.
   Also we examined the developmental changes in the sensitivity to noxious stimuli in normal rats. The withdrawal responses to mechanical and heat stimuli were significantly higher in young rats than in adult rats. As the rats grew up, the responses to mechanical stimuli to the hind-paws by von Frey filaments gradually decreased and became almost stable after postnatal nine weeks.
   These results suggest that some immaturity in pain pathway may produce a high nociceptive sensitivity in young rats and the factors in a developmental process would be required for the onset of persisting pain behaviors in the myopathic chronic pain model.

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