Pain
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Comparative Study
Functional MRI of the brain detects neuropathic pain in experimental spinal cord injury.
Functional magnetic resonance imaging (fMRI) has been used to map cerebral activations related to nociceptive stimuli in rodents. Here, we used fMRI to investigate abnormally increased responses to noxious or innocuous stimuli, in a well-established rat model of chronic neuropathic pain induced by photochemical lumbar spinal cord injury. In this model, a subpopulation of rats exhibits allodynia-like hypersensitivity to mechanical and cold stimulation of the trunk area. ⋯ Identical electrical stimulation, applied on trunks of spinally injured hypersensitive and non-hypersensitive rats, evoked significantly higher responses in SI of the former than the latter. Although levels of fMRI signals in SI of the trunk territory were not significantly different between normal and spinally injured non-hypersensitive rats, the administration of naloxone significantly increased fMRI signals in the non-hypersensitive rats, but not in the normal rats. We conclude that increased activation of contralateral SI is a key feature of behavioural neuropathic pain in spinally injured rats and that fMRI is an effective method to monitor experimental neuropathic pain in small animals.
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Comparative Study
Propentofylline attenuates allodynia, glial activation and modulates GABAergic tone after spinal cord injury in the rat.
In this study, we evaluated whether propentofylline, a methylxanthine derivative, modulates spinal glial activation and GABAergic inhibitory tone by modulation of glutamic acid decarboxylase (GAD)(65), the GABA synthase enzyme, in the spinal dorsal horn following spinal cord injury (SCI). Sprague-Dawley rats (225-250 g) were given a unilateral spinal transverse injury, from dorsal to ventral, at the T13 spinal segment. Unilateral spinal injured rats developed robust bilateral hindlimb mechanical allodynia and hyperexcitability of spinal wide dynamic range (WDR) neurons in the lumbar enlargement (L4-L5) compared to sham controls, which was attenuated by intrathecal (i.t.) administration of GABA, dose-dependently (0.01, 0.1, 0.5 microg). ⋯ Intrathecal treatment with propentofylline (PPF 10 mM) significantly attenuated the astrocytic and microglial soma hypertrophy and mechanical allodynia (p<0.05). Additionally, the Western blotting and immunohistochemistry data demonstrated that i.t. treatment of PPF significantly prevented the decrease of GAD(65) expression in both sides of the lumbar dorsal horn following SCI (p<0.05). In conclusion, our present data demonstrate that propentofylline modulates glia activation and GABAergic inhibitory tone by modulation of GAD(65) protein expression following spinal cord injury.
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Comparative Study
Endogenous kappa-opioid receptor systems inhibit hyperalgesia associated with localized peripheral inflammation.
Peripheral inflammation evokes functional and biochemical changes in the periphery and spinal cord which result in central sensitization and hypersensitivity. Inhibitory control systems from the rostral ventromedial medulla (RVM) are also activated. The present study investigates whether endogenous kappa-opioid receptor (KOPr) systems contribute to these neuroadaptations. ⋯ These data demonstrate a previously unrecognized role of endogenous KOPr systems in inhibiting hyperalgesia during inflammation. Furthermore, they demonstrate that decreased KOPr activity in either the spinal cord or RVM not only enhances mechanical and thermal hyperalgesia of the inflamed limb but also leads to an unmasking of mechanical hyperalgesia at a site remote from inflammation. The differential effects of KOPr antagonism on mechanical versus thermal thresholds for the non-inflamed paw support the notion that distinct neuroanatomical or neurochemical mechanisms modulate the processing of thermal versus mechanical stimuli.
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The mechanisms of nociception in the low back are poorly understood, partly because systematic recordings from dorsal horn neurons with input from the low back are largely missing. The purpose of this investigation was to (1) identify spinal segments and dorsal horn neurons receiving input from the low back, (2) test the effect of nerve growth factor (NGF) injected into the multifidus muscle (MF) on the neurons' responsiveness, and (3) study the influence of a chronic MF inflammation on the responses. In rats, microelectrode recordings were made in the segments L2, L3, and L5 to find dorsal horn neurons having input from the low back (LB neurons). ⋯ The centers of the neurons' receptive fields (RFs) were consistently located 2-3 segments caudally relative to their recording site. The results show that (1) input convergence from various tissues is common for LB neurons, (2) the input from structures of the low back is processed 2-3 segments cranially relative to the vertebral level of the RFs, and (3) the responsiveness of LB neurons is increased during a pathologic alteration of the MF. The above findings may be relevant for some cases of chronic low back pain in patients.
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Randomized Controlled Trial Multicenter Study
Exposure in vivo versus operant graded activity in chronic low back pain patients: results of a randomized controlled trial.
Since pain-related fear may contribute to the development and maintenance of chronic low back pain (CLBP), an exposure in vivo treatment (EXP) was developed for CLBP patients. We examined the effectiveness as well as specific mediating mechanisms of EXP versus operant graded activity (GA) directly and 6 months post-treatment in a multi-centre randomized controlled trial. In total, 85 patients suffering from disabling non-specific CLBP reporting at least moderate pain-related fear were randomly allocated to EXP or GA. ⋯ Furthermore, the effect of EXP relative to GA on functional disability and main complaints was mediated by decreases in catastrophizing and perceived harmfulness of activities. In sum, this study demonstrates that up to 6 months after treatment EXP is an effective treatment, but not more effective than GA, in moderately to highly fearful CLBP patients, although its superiority in altering pain catastrophizing and perceived harmfulness of activities is clearly established. Possible explanations for these findings are discussed.