Articles: neuralgia.
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Development of neuropathic pain occurs in a major portion of traumatic spinal cord injury (SCI) patients, resulting in debilitating and often long-term physical and psychological burdens. Following SCI, chronic dysregulation of extracellular glutamate homeostasis has been shown to play a key role in persistent central hyperexcitability of superficial dorsal horn neurons that mediate pain neurotransmission, leading to various forms of neuropathic pain. Astrocytes express the major CNS glutamate transporter, GLT1, which is responsible for the vast majority of functional glutamate uptake, particularly in the spinal cord. ⋯ Compared to both contusion-only animals and injured mice that received AAV8-eGFP control injection, AAV8-GLT1 delivery increased GLT1 protein expression in astrocytes of the injured cervical spinal cord dorsal horn, resulting in a significant and persistent reversal of already-established heat hypersensitivity. Furthermore, AAV8-GLT1 injection significantly reduced expression of the transcription factor and marker of persistently increased neuronal activation, ΔFosB, in superficial dorsal horn neurons. These results demonstrate that focal restoration of GLT1 expression in the superficial dorsal horn is a promising target for treating chronic neuropathic pain following SCI.
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Anesthesia and analgesia · Mar 2016
Electroacupuncture Relieves Nerve Injury-Induced Pain Hypersensitivity via the Inhibition of Spinal P2X7 Receptor-Positive Microglia.
Electroacupuncture (EA) has therapeutic effects on neuropathic pain induced by nerve injury; however, the underlying mechanisms remain unclear. In this study, we examined whether EA treatment relieves pain hypersensitivity via the down-regulation of spinal P2X7 receptor-positive (P2X7R⁺) microglia-mediated overexpression of interleukin (IL)-1β and/or IL-18. ⋯ EA treatment relieves nerve injury-induced tactile allodynia and thermal hyperalgesia via the inhibition of P2X7R⁺ microglia-mediated IL-1β overexpression.
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Clinical studies show that chronic pain can spread to adjacent or even distant body regions in some patients. However, little is known about how this happens. In this study, we found that partial infraorbital nerve transection (p-IONX) in MRL/MPJ mice induced not only marked and long-lasting orofacial thermal hyperalgesia but also thermal hyperalgesia from day 3 postoperatively (PO) and tactile allodynia from day 7 PO in bilateral hind paws. ⋯ In addition, microglial activation after p-IONX transmitted caudally from the Vc in the medulla to lumber dorsal horn in a time-dependent manner. Inhibition of microglial activation by minocycline at early but not late stage after p-IONX postponed and attenuated pain sensitization in the hind paw. These results indicate that neuropathic pain after p-IONX in MRL/MPJ mice spreads from the orofacial region to distant somatic regions and that a rostral-caudal transmission of central sensitization in the spinal cord is involved in the spreading process of pain hypersensitivity.
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Randomized Controlled Trial Multicenter Study
Pregabalin in Subjects With Painful Diabetic Peripheral Neuropathy Using an NSAID for Other Pain Conditions: A Double-Blind Crossover Study.
To evaluate pregabalin's efficacy and safety versus placebo to reduce pain in patients with diabetic peripheral neuropathy (DPN) using a concomitant nonsteroidal anti-inflammatory drug. ⋯ Pregabalin (vs. placebo) showed overall improvements in sleep, pain reduction in 1 sensitivity analysis, and was well tolerated. Potential factors that may have confounded the ability to detect a treatment difference in DPN pain reduction (high placebo response, carryover effect, short washout period, or pregabalin dose) are discussed in the context of future studies.