European journal of pain : EJP
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Because of its severity, chronicity, resistance to usual therapy and its consequences on quality of life, neuropathic pain represents a real clinical challenge. Fundamental research on this pathology uses metabolic, pharmacological or traumatic models in rodents that reproduce the characteristic human pain symptoms. In 1996, Mosconi and Kruger morphologically described a model of peripheral neuropathy in which a cuff of polyethylene tubing was placed around the sciatic nerve in rats. ⋯ The analysis of video recordings revealed that most aspects of spontaneous behavior remained unaffected on the long term, excepted for a decrease in the time spent at social interaction for the neuropathic mice. Using the elevated plus-maze and the marble-burying test, we also showed that neuropathic mice develop an anxiety phenotype. Our data indicate that sciatic nerve cuffing in mice is a pertinent model for the study of nociceptive and emotional consequences of sustained neuropathic pain.
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Comparative Study
Pain, disability and coping reflected in the diurnal cortisol variability in patients scheduled for lumbar disc surgery.
Symptoms of lumbar disc herniation can be induced by both mechanical compression of the nerve roots and by biochemical irritants from the disc tissues. Proinflammatory cytokines, as well as stress are potent stimulators of the hypothalamic-pituitary-adrenal axis, reflected in enhanced release of cortisol from the adrenal cortex. Altered cortisol production is also associated to behaviour and coping patterns. The aim of the present study was to explore the relation between pain, physical function, psychosocial factors and quality of life to the diurnal cortisol variability, in patients with lumbar disc herniation. ⋯ Patients with lumbar disc herniation and a low diurnal cortisol variability had lower physical function, perceived lower possibilities of influencing their pain, and were more prone to catastrophise than patients with lumbar disc herniation and a high diurnal cortisol variability.
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Phosphorylation of the N-methyl-D-aspartate (NMDA) receptor NR1 subunit (pNR1) in the spinal cord is associated with increased neuronal responsiveness, which underlies the process of central sensitization. Because of the importance of NR1 in central sensitization, the first goal of this study was to examine both time- and lamina-dependent changes in spinal NR1 and pNR1 expression in a chronic constriction injury (CCI) model of neuropathic pain. Increased excitability of capsaicin sensitive primary afferents (CSPAs), which express TRPV1 receptors, also contributes to central sensitization. ⋯ Pretreatment with RTX (0.3mg/kg, s.c. in the scruff of the neck or intraplantar) 2 days prior to CCI completely prevented induction of thermal hyperalgesia, but not mechanical allodynia in neuropathic rats. Interestingly, RTX treatment significantly attenuated the CCI-induced upregulation of NR1 and pNR1 in spinal laminae I-II and V-VI, but not laminae III-IV as compared with that of vehicle-treated CCI rats. These findings demonstrate that the increased expression of NR1 and pNR1 in spinal laminae I-II and V-VI is dependent on activation of CSPAs, which ultimately contribute to the development of thermal hyperalgesia in neuropathic rats.
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Voltage-gated sodium channels play an essential role in regulating the excitability of nociceptive primary afferent neurones. In particular the tetrodotoxin-sensitive (TTX-S) Na(V)1.7 and the tetrodotoxin-resistant (TTX-R) Na(V)1.8 and Na(V)1.9 channels have been suggested to play a role in inflammatory pain. Previous work has revealed acute administration of inflammatory mediators, such as Freund's complete adjuvant (FCA) or carrageenan caused an upregulation in the levels of Na(V)1.7 and Na(V)1.8 protein in DRG (dorsal root ganglia) tissue up to 4 days post-insult. ⋯ The results demonstrate that, following FCA injection, Na(V)1.9 expression is upregulated at days 14, 21 and 28 post-FCA, with Na(V)1.7 and Na(V)1.8 showing increased channel expression at days 14 and 28. These observations are accompanied by a unilateral joint hypersensitivity in the FCA-injected knee indicated by a behavioural shift in weight distribution measured using an incapacitance tester. The increased presence of these channels suggests that Na(V)1.7, Na(V)1.8 and Na(V)1.9 play a role, at least in part, in the maintenance of chronic inflammatory pain several weeks after the initial insult.
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Comparative Study
Intrathecal antinociceptive interaction between the NMDA antagonist ketamine and the opioids, morphine and biphalin.
Biphalin is an opioid peptide analogue that currently is under clinical development as a new type of site-directed analgesic. In rats, the intrathecal (i.t.) analgesic potency of biphalin is 1000-fold greater than morphine. Such a high activity may reflect this compound's activation of three types of opioid receptors (mu, delta and kappa). ⋯ Co-administration of ketamine with biphalin or morphine produced markedly greater antinociception than biphalin or morphine alone in acute, thermal tail flick testing. These results suggest that NMDA antagonists may be useful potentiators of biphalin analgesia. Thus, to obtain the same spinal antinociceptive effect, lower doses of biphalin or morphine are required when ketamine is co-administered.