Pain
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Patients with chronic pain often have accompanying cognitive deficiency, which may reduce their quality of life and hamper efficient medical treatment. Alteration of extracellular glycine concentration may affect cognitive function and spinal pain signaling. In the present study, we assessed recognition memory by novel-object recognition and found that mice developing mechanical hypersensitivity after peripheral nerve injury exhibited impaired recognition ability for novelty, which was never observed in mice provided the selective glycine transporter 1 (GlyT1) inhibitor N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl]sarcosine (NFPS) systemically. ⋯ These findings imply that chronic pain has a crucial influence on hippocampal plasticity related to cognitive function, and strongly suggest that increasing the extracellular level of glycine via blockade of GlyT1 is a potential therapeutic approach for chronic pain with memory impairment. Chronic pain crucially influences hippocampal plasticity related to cognitive function. Increasing the extracellular level of glycine via blockade of GlyT1 is a potential therapeutic approach for chronic pain with memory impairment.
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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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Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). While the primary symptoms of MS are losses of sensory and motor functions, it is now recognized that chronic pain is also a major concern affecting between 50% and 80% of MS patients. To date, however, few studies have examined the underlying mechanisms of chronic pain in MS or in the animal model, experimental autoimmune encephalomyelitis (EAE), which shares many features of MS pathology. ⋯ There is, however, a significant influx of CD3+ T cells and increased astrocyte and microglia/macrophage reactivity in the superficial dorsal horn of mice with MOG(35-55) EAE. This suggests that inflammation and reactive gliosis may be key mediators of allodynia in MOG(35-55) EAE similar to peripheral nerve and spinal cord injury models. Taken together, our results show that the MOG(35-55) EAE model is a useful tool to study neuropathic pain in MS.
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Comparative Study
Effects of amitriptyline and gabapentin on bilateral hyperalgesia observed in an animal model of unilateral axotomy.
Nociceptive responses in an animal model of peripheral nerve injury were studied. The left common sciatic nerve was exposed, tightly ligated at two locations and transected between the ligatures. A bilateral decrease in the nociceptive threshold to mechanical stimulation was observed within 3 h after the operation. ⋯ Similar bilateral hyperalgesia was observed when axotomy was performed using silk thread instead of chromic gut. When this axotomy model was applied to mice, the nociceptive thresholds in both paws immediately showed a significant decrease in the same manner as in rats. The bilateral and systemic hyperalgesia observed in this axotomy model, which resembles the clinical features of chronic neuropathic pain, suggests the involvement of the central nervous system in the maintenance of the chronic pain state.