Pain
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Randomized Controlled Trial
An investigation of the development of analgesic tolerance to TENS in humans.
Transcutaneous electrical nerve stimulation (TENS) is a noninvasive modality used to control pain. Animal models show that repeated TENS application produces analgesic tolerance and cross-tolerance at spinal opioid receptors. The aim of the present investigation was to examine whether repeated application of TENS produces analgesic tolerance in humans. ⋯ These data suggest that repeated daily application of TENS results in a decrease in its hypoalgesic effect by the fifth day and that the tolerance-like effect to repeated TENS results from tolerance at centrally located opioid receptors. The lack of change in DNIC response suggests that TENS and DNIC utilize separate pathways to produce analgesia. Repeated high-frequency and low-frequency transcutaneous electrical nerve stimulation produce analgesic tolerance in humans by the fourth and fifth day of treatment, respectively.
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It was previously reported that in 5 patients with small-fiber neuropathy, neuropathic pain, and hyperalgesia, application of a single, brief electrical stimulus to the skin could give rise to 2 afferent impulses in a C-nociceptor fiber. These double spikes, which are attributed to unidirectional conduction failure at branch points in the terminal arborisation, provide a possible mechanism for hyperalgesia. We here report that similar multiple spikes are regularly observed in 3 rat models of neuropathic pain: nerve crush, nerve suture, and chronic constriction injury. ⋯ Whereas only double spikes had previously been described in patients, in these more extensive recordings from rats we found that triple spikes could also be observed after a single electrical stimulus. The results strengthen the suggestion that multiple spiking, because of impaired conduction in the terminal branches of nociceptors, may contribute to hyperalgesia in patients with neuropathic pain. Double and triple spikes in c-nociceptors, caused by impaired conduction in terminal branches, may be an important cause of hyperalgesia in patients with neuropathic pain.
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Randomized Controlled Trial
Transcutaneous spinal cord direct current stimulation inhibits the lower limb nociceptive flexion reflex in human beings.
Aiming at developing a new, noninvasive approach to spinal cord neuromodulation, we evaluated whether transcutaneous direct current (DC) stimulation induces long-lasting changes in the central pain pathways in human beings. A double-blind crossover design was used to investigate the effects of anodal direct current (2mA, 15min) applied on the skin overlying the thoracic spinal cord on the lower-limb flexion reflex in a group of 11 healthy volunteers. To investigate whether transcutaneous spinal cord DC stimulation (tsDCS) acts indirectly on the nociceptive reflex by modulating excitability in mono-oligosynaptic segmental reflex pathways, we also evaluated the H-reflex size from soleus muscle after tibial nerve stimulation. ⋯ None of our subjects reported adverse effects after active stimulation. These results suggest that tsDCS holds promise as a tool that is complementary or alternative to drugs and invasive spinal cord electrical stimulation for managing pain. Thoracic transcutaneous direct current stimulation induces depression of nociceptive lower limb flexion reflex in human beings that persists after stimulation offset; this form of stimulation holds promise as a tool that is complementary or alternative to drugs and invasive spinal cord electrical stimulation for managing pain.
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Comparative Study
TNF-α in CRPS and 'normal' trauma--significant differences between tissue and serum.
Posttraumatic TNF-alpha signaling may be one of the factors responsible for pain and hyperalgesia in complex regional pain syndromes (CRPS). In order to further specify the role of TNF-alpha we investigated tissue (skin) and serum concentrations in three different patient groups: patients with osteoarthritis and planned surgery, with acute traumatic upper limb bone fracture waiting for surgery, and with CRPS I. Thirty patients (10 in each group) were recruited. ⋯ In contrast, serum TNF-alpha values were the same in osteoarthritis and CRPS, and lower in fracture patients (p<0.03). Our results indicate a local but not systemic increase of TNF-alpha in CRPS patients. This increase persists for months after limb trauma and may offer the opportunity for targeted treatment.
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Comparative Study
Intraepidermal nerve fiber loss corresponds to the development of taxol-induced hyperalgesia and can be prevented by treatment with minocycline.
Loss of intraepidermal nerve fibers (IENFs) has been speculated to play a critical role in the development of various neuropathies. In this study, the density of IENFs were studied over time during the induction of Taxol (Bristol-Myers Squibb, NY, USA)-induced chemoneuropathy and compared with the changes in IENFs in animals co-treated with Taxol plus the protective agent minocycline. Rats were injected (intraperitoneally) with 2mg/kg of Taxol every other day for four injections (day 1, 3, 5, and 7). ⋯ Animals receiving minocycline plus Taxol showed no hyperalgesia or loss of IENFs. This study confirms, for the first time, that a loss of IENFs occurs as a neuropathy develops, and further shows a protection against both IENF loss and hyperalgesia with minocycline treatment. The progression of Taxol-induced mechanical hypersensitivity coincides with loss of intraepidermal nerve fibers, and the hyperalgesia and nerve fiber loss were prevented with minocycline treatment.