Articles: neuropathic-pain.
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Neuropathic pain (NP) continues to be challenging to treat due to lack of effective drugs. Accumulating evidence elucidated that glia-mediated inflammatory reactions play a pivotal role in the introduction and development of NP. Besides, activation of the c-Jun N-terminal kinase (JNK)/monocyte chemoattractant protein-1 (MCP-1) pathway in astrocytes has been reported to be critical for spinal astrocytic activation and neuropathic pain development after spinal nerve ligation (SNL). Tanshinone IIA, a major active component of a traditional Chinese drug, Danshen, possesses potent immuno-suppressive activities. The present study was undertaken to assess whether intraperitoneal administration of tanshinone IIA sulfonate (TIIAS) has analgesic effect on SNL-induced neuropathic pain and whether the inhibition of astrocytic activation and JNK/MCP-1 pathway is involved in the analgesic effect of TIIAS. ⋯ The present results suggest that the analgesic effects of TIIAS in neuropathic pain are mainly mediated by the down-regulation of SNL-induced astrocytic activation, which is via the inhibition of JNK/MCP-1 pathway.
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Neuroscience letters · Mar 2015
Urinary trypsin inhibitor attenuates the development of neuropathic pain following spinal nerve ligation.
Following nerve injury, inflammatory and algesic mediators are released. This neuroinflammatory outbreak causes neuronal damage and chronic neuropathic pain. Urinary trypsin inhibitor (ulinastatin, UTI), which has anti-inflammatory properties and neuroprotective effects, is used to lower the levels of inflammatory factors during surgery. ⋯ The paw withdrawal threshold was significantly increased in the rats from group U pre compared with the rats from groups N and U post until the 7th post-SNL day (P<0.05). The levels of IL-6 also were significantly decreased in the rats from group U pre compared with the rats from group N and U post until the 7th post-SNL day (P<0.05). Ulinastatin increased the paw withdrawal threshold following SNL when it was administered before the development of neuropathic pain, and may attenuate the development of neuropathic pain.
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Spinal cord injury (SCI) is a devastating medical condition affecting 1.2 million people in the United States. Central neuropathic pain is one of the most common medical complications of SCI. Current treatment options include opioids, antiepileptic agents such as gabapentin, antispastic agents such as baclofen or tizanidine, and tricyclic acid. ⋯ A combination of approaches, from standard general pain assessments to medically specific questions unique to SCI pathophysiology, is essential for this population. A multidisciplinary approach to patient care, in addition with a better understanding of pathophysiology and diagnosis, will lead to improved management and treatment of patients with SCI displaying central neuropathic pain. Here we summarize the most recent classification tools, pathophysiology, and current treatment options for patients with SCI with central neuropathic pain.
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Electrical stimulation of low-threshold Aβ-fibers (Aβ-ES) is used clinically to treat neuropathic pain conditions that are refractory to pharmacotherapy. However, it is unclear how Aβ-ES modulates synaptic responses to high-threshold afferent inputs (C-, Aδ-fibers) in superficial dorsal horn. Substantia gelatinosa (SG, lamina II) neurons are important for relaying and modulating converging spinal nociceptive inputs. ⋯ These findings show that activities in Aβ-fibers lead to frequency-dependent depression of synaptic transmission in SG neurons in response to peripheral noxious inputs. However, 50 Hz Aβ-ES failed to induce cell-type selective inhibition in SG neurons. The physiologic implication of this novel form of synaptic depression for pain modulation by Aβ-ES warrants further investigation.
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Neuroscience letters · Mar 2015
Possible involvement of activated locus coeruleus-noradrenergic neurons in pain-related sleep disorders.
The locus coeruleus (LC) is a noradrenergic brainstem structure that is considered to play a role in promoting arousal. To further clarify the role of LC noradrenergic neurons, we performed an optogenetic assay by injecting AAV-channelrhodopsin-2 (ChR2) into the LC of cre-tyrosine hydrolase (TH) mice. We found here that the specific activation of LC noradrenergic neurons produced a significant increase in wakefulness and a significant decrease in non-rapid eye movement (NREM) sleep during photostimulation. ⋯ In the present study, sciatic nerve ligation, which produced significant thermal hyperalgesia, significantly increased the levels of noradrenaline released in the prefrontal cortex (PFC) by the weak electrical stimulation of neurons in the LC. Under these conditions, the systemic administration of adrenaline α and β inhibitor cocktail at 7 days after sciatic nerve ligation restored the increased wakefulness and decreased NREM sleep to normal levels. These results suggest that neuropathic pain may accelerate neurons in the LC, and its overactivation may be, at least in part, associated with sleep disturbance under neuropathic pain.