Pain
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Comparative Study
Spinal NK-1 receptor expressing neurons mediate opioid-induced hyperalgesia and antinociceptive tolerance via activation of descending pathways.
Opioids can induce hyperalgesia in humans and in animals. Mechanisms of opiate-induced hyperalgesia and possibly of spinal antinociceptive tolerance may be linked to pronociceptive adaptations occurring at multiple levels of the nervous system including activation of descending facilitatory influences from the brainstem, spinal neuroplasticity, and changes in primary afferent fibers. Here, the role of NK-1 receptor expressing cells in the spinal dorsal horn in morphine-induced hyperalgesia and spinal antinociceptive tolerance was assessed by ablating these cells with intrathecal injection of SP-saporin (SP-SAP). ⋯ Thus, NK-1 receptor expressing neurons play a critical role in sustained morphine-induced neuroplastic changes which underlie spinal excitability reflected as thermal and tactile hypersensitivity to peripheral stimuli, and to reduced antinociceptive actions of spinal morphine (i.e., antinociceptive tolerance). Ablation of these cells likely eliminates the ascending limb of a spinal-bulbospinal loop that engages descending facilitation and elicits subsequent spinal neuroplasticity. The data may provide a basis for understanding mechanisms of prolonged pain which can occur in the absence of tissue injury.
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Comparative Study
New evidence for the involvement of spinal fractalkine receptor in pain facilitation and spinal glial activation in rat model of monoarthritis.
Fractalkine, a chemokine binding to only one known receptor CX3CR1, has recently been proposed to be a neuron-to-glia signal in the spinal cord leading to microglial activation and glially dependent pain facilitation. The previous studies explored that blockade of endogenous fractalkine, using anti-CX3CR1 neutralizing antibody, dose-dependently attenuated neuropathic pain. The present study examined the role of endogenous fractalkine in inflammatory pain. ⋯ Intrathecal injection of anti-CX3CR1 neutralizing antibody both delayed the development of mechanical allodynia and thermal hyperalgesia, and reversed established pain facilitation. Furthermore, blockade of CX3CR1 significantly suppressed activation of spinal glia, especially microglia, evoked by MA. These data provided new evidence for the contribution of endogenous fractalkine to the initiation and early maintenance of inflammatory pain facilitation via activating spinal microglia.
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The dorsal column pathway consists of direct projections from primary afferents and of ascending fibers of the post-synaptic dorsal column (PSDC) cells. This pathway mediates touch but may also mediate allodynia after nerve injury. The role of PSDC neurons in nerve injury-induced mechanical allodynia is unknown. ⋯ Retrogradely labeled DRG cells of nerve injured rats were large diameter neurons, which expressed NPY, but no detectable CGRP or substance P. Spinal nerve injury sensitizes neurons in the spinal dorsal horn to repetitive light touch but PSDC neurons apparently do not participate in touch-evoked allodynia. Sensitization of these non-PSDC neurons may result in activation of projections integral to the spinal/supraspinal processing of enhanced pain states and of descending facilitation, thus priming the central nervous system to interpret tactile stimuli as being aversive.
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Randomized Controlled Trial Comparative Study Clinical Trial
Differential effect of intravenous S-ketamine and fentanyl on atypical odontalgia and capsaicin-evoked pain.
Atypical odontalgia (AO) is an intraoral pain condition of currently unknown mechanisms. In 10 AO patients and 10 matched healthy controls, we examined the effect of intravenous infusion of an N-methyl-D-aspartate (NMDA) receptor antagonist S-ketamine and a mu-opioid agonist fentanyl on spontaneous AO pain and on an acute intraoral nociceptive input evoked by topical application of capsaicin. The drugs were administered in a randomized, placebo-controlled, cross-over manner. ⋯ No side-to-side differences in QST measures were found in AO patients. The present study demonstrates that AO is unlikely to be primarily due to a persistent afferent barrage from the peripheral region. Furthermore, in contrast to studies on various neuropathic pain conditions, fentanyl and S-ketamine in the present doses failed to attenuate AO pain.
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Randomized Controlled Trial Comparative Study Clinical Trial
Does the presence of sensory hypersensitivity influence outcomes of physical rehabilitation for chronic whiplash?--A preliminary RCT.
Patients with chronic whiplash associated disorders present with varied sensory, motor and psychological features. In this first instance it was questioned whether a multimodal program of physical therapies was an appropriate management to be broadly prescribed for these patients when it was known that some would have sensory features suggestive of a notable pain syndrome. A randomised controlled trial was conducted with 71 participants with persistent neck pain following a motor vehicle crash to explore this question. ⋯ Even with the presence of sensory hypersensitivity in 72.5% of subjects, both groups reported some relief of neck pain and disability (Neck Disability Index) and it was superior in the group receiving multimodal physiotherapy (p=0.04). Post-hoc observations however suggested that relief was marginal in the subgroup with both widespread mechanical and cold hyperalgesia. Further research is required to test the validity of this sub-group observation and to test the effect of the intervention in the long term.