European journal of pain : EJP
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Endogenous analgesia (EA) can be examined experimentally using a conditioned pain modulation (CPM) paradigm. While noxious conditioning stimulation intensities (CSIs) are mainly used, it has not been fully investigated in the same experimental design whether the experienced conditioning pain level affects CPM responses. The principal goal of the present study was to characterize CPM induction and magnitudes evoked by various conditioning pain levels. ⋯ Conditioning pain levels were correlated across all CSIs, as were CPM magnitudes (Ps ≤ 0.01). We conclude that among males, (i) once a CPM response is evoked by a required conditioning pain experience, its magnitude is not further affected by increasing conditioning pain and (ii) CPM magnitudes are inter-correlated, but unrelated to conditioning pain reports. These observations may suggest that CPM responses represent an intrinsic element of an individual's EA processes, which are not significantly affected by the experienced conditioning pain.
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Previous studies showed that triptans and other 5-HT(1B/1D)-receptor agonists attenuate hyper-responsiveness to mechanical stimulation of the face in a rat model of trigeminal neuropathic pain, probably by activating 5-HT(1B/1D)-receptors on primary afferent nociceptive fibers. We now tested whether blockade of post-synaptic receptors for the excitatory amino acid glutamate released by these fibers would increase this action. We thus evaluated whether (±)1-hydroxy-3-aminopyrrolidine-2-one (HA-966), an antagonist at the glycine/D-serine site of N-methyl-D-aspartate (NMDA)-receptors, would potentiate the anti-allodynic action of dihydroergotamine and zolmitriptan in rats with chronic constriction injury to the infraorbital nerve (CCI-ION). ⋯ HA-966 (2.5mg/kg, s.c.), inactive on its own, enhanced the anti-allodynic effects of dihydroergotamine (eightfold increase) and zolmitriptan (threefold increase) in CCI-ION rats, but these drugs exerted no effects in allodynic CCI-SN rats. NMDA-receptor blockade by memantine (5mg/kg, i.p.) also enhanced, whereas activation at glycine/NMDA site by D-cycloserine (3mg/kg, i.p.) reduced the anti-allodynic properties of zolmitriptan in CCI-ION rats. Combined administration of NMDA-receptor antagonist and 5-HT(1B/1D)-receptor agonist may be a promising approach for alleviating trigeminal neuropathic pain.
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Eighteen patients with peripheral neuropathic pain (PNeP) and seven patients with central post-stroke pain (CPSP) all suffering from dynamic mechanical allodynia (DMA) in a limb were studied. From recent research it is reasonable to suggest that A-beta fibres constitute the peripheral substrate for DMA in patients with PNeP. The pathophysiological basis for DMA in patients with CPSP is unknown. ⋯ The rest of the patients lost DMA without transition to DMD. The transition or loss of DMA without transition occurred early and concurrently in time during the block and was paralleled by a continuous impairment of mainly A-beta fibre function. We therefore suggest DMA to be the hyperbole of DMD, the difference being the number of mechanoreceptive fibres having access to the nociceptive system.
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It has been reported that the whisker pad (WP) area, which is innervated by the second branch of the trigeminal nerve, shows allodynia/hyperalgesia following transection of the mental nerve (MN: the third branch of the trigeminal nerve). However, the mechanisms of this extra-territorial pain induction still remain unclear. Glia and cytokines are known to facilitate perception of noxious input, raising a possibility that these non-neuronal elements are involved in the induction and spread of allodynia/hyperalgesia at non-injured skin territory. ⋯ Administration of a noncompetitive antagonist of NMDA receptors MK-801 (i.t., 5 μg/rat) reversed allodynia/hyperalgesia. IL-1 receptor type I (IL-1RI) was localized in Fos- and phospho NR1-immunoreactive neurons. These results suggest that IL-1beta in the Vc plays an important role in the development of extra-territorial tactile allodynia/hyperalgesia after MN transection.