Pain
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Various animal models of neuropathic pain have been developed which involve creating a lesion in a spinal root. We describe a human correlate in which patients developed a neuropathic pain syndrome after having one spinal nerve surgically divided. In some patients with brachial plexus lesions, the C7 spinal nerve from the opposite side is divided and used as a nerve transfer to re-innervate the injured brachial plexus. ⋯ The pain and hyperalgesia persisted during a phentolamine infusion, which produced a sympathetic blockade. Only mild parasthesia persisted at a 1 year follow up. Thus, surgical division of a single spinal nerve in humans can lead to the development of neuropathic pain.
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Vulvar vestibulitis syndrome (VVS) is a common cause of dyspareunia in pre-menopausal women. Little is known about sensory function in the vulvar vestibule, despite Kinsey's assertion that it is important for sexual sensation. We examined punctate tactile and pain thresholds to modified von Frey filaments in the genital region of women with VVS and age- and contraceptive-matched pain-free controls. ⋯ Women with VVS reported significantly more catastrophizing thoughts related to intercourse pain, but there was no difference between groups in catastrophizing for unrelated pains. Pain intensity ratings for stimuli above the pain threshold increased in a parallel fashion with log stimulus intensity in both groups, but the ratings of distress were substantially greater in the VVS group than in controls at equivalent levels of pain intensity. The data imply that VVS may reflect a specific pathological process in the vestibular region, superimposed on systemic hypersensitivity to tactile and pain stimuli.
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Comparative Study
Neurogenic hyperalgesia versus painful hypoalgesia: two distinct mechanisms of neuropathic pain.
Patients with sensory disturbances of painful and non-painful character show distinct changes in touch and/or pain sensitivity. The patterns of sensory changes were compared to those of human surrogate models of neuropathic pain to assess the underlying mechanisms. We investigated 30 consecutive in-patients with dysaesthesia of various origins (peripheral, spinal, and brainstem lesions) and 15 healthy subjects. ⋯ Our findings suggest that neuropathic pain is based on two distinct mechanisms: (I) central sensitization (neurogenic hyperalgesia; in patients with minor sensory impairment) and (II) partial nociceptive deafferentation (painful hypoalgesia; in patients with major sensory deficit). This distinction as previously postulated for postherpetic neuralgia, is obviously valid also for other conditions. Our findings emphasize the significance of a mechanism-based classification of neuropathic pain.
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N-type calcium channels modulate the release of key pro-nociceptive neurotransmitters such as glutamate and substance P (SP) in the central nervous system. Considerable research interest has focused on the therapeutic potential of the peptidic omega-conopeptides, GVIA and MVIIA as novel analgesic agents, due to their potent inhibition of N-type calcium channels. Recently, the novel peptidic N-type calcium channel blocker, AM336, was isolated from the venom of the cone snail, Conus catus. ⋯ Following acute i.t. dosing, AM336 evoked dose-dependent antinociception (ED50 approximately 0.110 nmol) but the doses required to produce side-effects were an order of magnitude larger than the doses required to produce antinociception. For i.t. doses of MVIIA
0.07 nmol, produced a dose-dependent decrease in antinociception but the incidence and severity of the side-effects continued to increase for all doses of MVIIA investigated, suggesting that dose-titration with MVIIA in the clinical setting, may be difficult. -
The aim of this study was to develop a rat model of capsaicin-induced pain in the orofacial region. We examined the effects of subcutaneous injection of different doses of capsaicin (0.25, 0.4, 0.8, 1.5, 2.5, 25, 50, 100, 500 microg) on the face-grooming response. Injection of capsaicin into the vibrissa pad produced an immediate grooming of the injected area with ipsilateral fore- or hindpaw. ⋯ The local administration of morphine (ED(50): 0.65 mg/kg) was more potent than systemic injection (ED50: 2.54 mg/kg) in reducing the grooming behavior. In conclusion, the orofacial capsaicin test appears to be a valid and reliable method for studying trigeminal pain mechanisms and testing analgesic drugs. The results of the present study also support the clinical use of peripheral opioid administration for the treatment of orofacial painful conditions.