The Journal of neuroscience : the official journal of the Society for Neuroscience
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Reactive oxygen species contribute to ischemic brain injury. This study examined whether the porphyrin catalytic antioxidant manganese (III) meso-tetrakis (N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP(5+)) reduces oxidative stress and improves outcome from experimental cerebral ischemia. Rats that were subjected to 90 min focal ischemia and 7 d recovery were given MnTE-2-PyP(5+) (or vehicle) intracerebroventricularly 60 min before ischemia, or 5 or 90 min or 6 or 12 hr after reperfusion. ⋯ There was no effect of 150 or 300 ng of MnTE-2-PyP(5+) pretreatment on selective neuronal necrosis resulting from 10 min forebrain ischemia and 5 d recovery in rats. Administration of a metalloporphyrin catalytic antioxidant had marked neuroprotective effects against focal ischemic insults when it was given up to 6 hr after ischemia. This was associated with decreased postischemic superoxide-mediated oxidative stress.
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The recently cloned vanilloid receptor (VR1) is postulated to account for heat and capsaicin sensitivity in unmyelinated afferents. We sought to determine whether heat and capsaicin sensitivity also coexist in myelinated nociceptive afferents. Action potential (AP) activity was recorded from single A-fiber nociceptors that innervated the hairy skin in monkey. ⋯ However, the largest response to capsaicin (314 +/- 98 APs in 10 min) was observed for five afferents that were insensitive to heat as well as mechanical stimuli and therefore may be classified as cutaneous chemoreceptors. These results suggest that A-fiber nociceptors play a role in the pain and hyperalgesia associated with capsaicin injection. Our finding that a subgroup of capsaicin-sensitive A-fiber nociceptors are insensitive to heat predicts the existence of heat-insensitive capsaicin receptors.
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The present study was designed to investigate the role of a protein kinase C (PKC) isoform in the uncoupling of the mu-opioid receptor from G-proteins after repeated intrathecal injection of a selective mu-receptor agonist, [D-Ala(2),N-MePhe(4),Gly-ol(5)]enkephalin (DAMGO), in the spinal cord of mice. The activation of G-proteins by opioids was measured by monitoring the guanosine-5'-o-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding. Mice were injected intrathecally with saline or DAMGO once a day for 1-7 d. ⋯ Western blotting analysis showed that chronic DAMGO treatment increased the levels of PKCgamma, but not PKCalpha, PKCbetaI, and PKCbetaII isoforms, in spinal cord membranes. Furthermore, mice lacking PKCgamma failed to exhibit the desensitization of the DAMGO-stimulated [(35)S]GTPgammaS binding after repeated DAMGO injection. These findings indicate that repeated intrathecal administration of DAMGO may activate the PKCgamma isoform and in turn cause a desensitization of mu-receptor-mediated G-protein activation in the mouse spinal cord.
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The peptide somatostatin [somatotropin release-inhibiting factor (SRIF)] is widely distributed in the body and exerts a variety of hormonal and neural actions. Several lines of evidence indicate that SRIF is important in nociceptive processing: (1) it is localized in a subset of small-diameter dorsal root ganglion cells; (2) activation of SRIF receptors results in inhibition of both nociceptive behaviors in animals and acute and chronic pain in humans; (3) SRIF inhibits dorsal horn neuronal activity; and (4) SRIF reduces responses of joint mechanoreceptors to noxious rotation of the knee joint. The goal of the present study is to show that cutaneous nociceptors are under the tonic inhibitory control of SRIF. ⋯ Electrophysiological recordings using an in vitro glabrous skin-nerve preparation show increased nociceptor activity in response to c-SOM, and this increase is blocked by the same three SRIF agonists. Parallel behavioral and electrophysiological studies using the opioid antagonist naloxone demonstrate that endogenous opioids do not maintain a tonic inhibitory control over peripheral nociceptors, nor does opioid receptor antagonism influence peripheral SRIF effects on nociceptors. These findings demonstrate that SRIF receptors maintain a tonic inhibitory control over peripheral nociceptors, and this may contribute to mechanisms that control the excitability of these terminals.
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Comparative Study Clinical Trial
Reorganization of motor and somatosensory cortex in upper extremity amputees with phantom limb pain.
Phantom limb pain (PLP) in amputees is associated with reorganizational changes in the somatosensory system. To investigate the relationship between somatosensory and motor reorganization and phantom limb pain, we used focal transcranial magnetic stimulation (TMS) of the motor cortex and neuroelectric source imaging of the somatosensory cortex (SI) in patients with and without phantom limb pain. For transcranial magnetic stimulation, recordings were made bilaterally from the biceps brachii, zygomaticus, and depressor labii inferioris muscles. ⋯ Neuroelectric source imaging revealed a similar medial displacement of the dipole center for face stimulation in patients with phantom limb pain. There was a high correlation between the magnitude of the shift of the cortical representation of the mouth into the hand area in motor and somatosensory cortex and phantom limb pain. These results show enhanced plasticity in both the motor and somatosensory domains in amputees with phantom limb pain.