European journal of pain : EJP
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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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Pain Management Programmes (PMPs) are a multi-disciplinary approach to the management of chronic low back pain (CLBP). Notwithstanding evidence of effectiveness, successful take-up of programmes requires acceptability to patients. We used a discrete choice experiment to investigate patient preferences for alternative PMPs for managing CLBP in primary care. ⋯ Probability of take-up increases when PMPs better reflect patient preferences. Given preferences, resource constraints, and evidence on clinical outcomes of alternative configurations it is suggested more resource-intensive PMPs be reserved for those with the most severe and disabling pain and less intensive programmes delivered over a longer time period in smaller groups for those with less severe pain. These findings can inform future randomised trials to evaluate acceptable PMPs in primary care.
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Comparative Study
Postnatal expression of the homeobox gene Prrxl1 (Drg11) is increased in inflammatory but not neuropathic pain.
The paired-type homeodomain transcription factor Prrxl1 (also known as Drg11) is a key regulator of the differentiation and survival of dorsal root ganglia (DRG) and spinal nociceptive neurons in pre- and perinatal stages. Prrxl1(-/-) mice exhibit abnormalities in DRG-spinal projections, defects in superficial dorsal horn structure and neurochemistry, and reduced nociceptive behaviour in several pain tests. Although a low expression of Prrxl1 persists in dorsal root ganglia beyond embryonic development, no data exist on its role in adult life. ⋯ Interestingly, the expression of the mRNA splice variant Prrxl1b was unchanged in both pain conditions. Immunohistochemical studies showed an increase in the number of Prrxl1-positive neurons in the inflammatory pain model, which belonged both in the peptidergic and non-peptidergic categories. Our present results point to a role for Prrxl1 in sensitization of nociceptive neurons upon inflammatory pain.
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The vast majority of human peripheral nerve injuries occur in the upper limb, whereas the most animal studies have been conducted using the hindlimb models of neuropathic pain, involving damages of the sciatic or lumbar spinal nerve(s). We attempted to develop a rat forelimb model of peripheral neuropathy by partial injury of the median and ulnar nerves. The halves of each nerve were transected by microscissors at about 5mm proximal from the elbow joint and behavioral signs of neuropathic pain, such as mechanical and cold allodynia, and heat hyperalgesia, were monitored up to 126 days following nerve injury. ⋯ These behaviors were significantly alleviated by administration of gabapentin (5 or 50mg/kg, i.p.) in a dose-dependent manner. Therefore, these abnormal sensitivities are interpreted as the signs of neuropathic pain following injury of the median and ulnar nerves. Our rat forelimb model of neuropathic pain may be useful for studying human neuropathic pain and screening for valuable drug candidates.