Articles: neuralgia.
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Patients with neuropathic pain often experience exaggerated pain and anxiety. Central sensitization has been linked with the maintenance of neuropathic pain and may become an autonomous pain generator. Conversely, emerging evidence accumulated that central sensitization is initiated and maintained by ongoing nociceptive primary afferent inputs. ⋯ Mechanistic analysis revealed that activation of PKG-I in nociceptors is responsible for synaptic potentiation in the anterior cingulate cortex upon peripheral neuropathy through presynaptic mechanisms involving brain-derived neurotropic factor signaling. Our results revealed that PKG-I expressed in nociceptors is a key determinant for cingulate synaptic plasticity after nerve injury, which contributes to the maintenance of pain hypersensitivity and anxiety. Thereby, this study presents a strong basis for opening up a novel therapeutic target, PKG-I, in nociceptors for treatment of comorbidity of neuropathic pain and anxiety with least side effects.
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Chemotherapy-induced peripheral neuropathic pain (CIPNP) often occurs in cancer patients treated with antineoplastic drugs. Therapeutic management of CIPNP is very limited, at least in part due to the largely unknown mechanisms that underlie CIPNP genesis. Here, we showed that systemic administration of the chemotherapeutic drug paclitaxel significantly and time-dependently increased the levels of cyclic AMP response element-binding protein (CREB) in dorsal root ganglion (DRG) neurons. ⋯ CREB overexpression also elevated the expression of DNMT3a in in vivo and in vitro DRG neurons of naïve mice. Given that DNMT3a is an endogenous instigator of CIPNP and that CREB co-expresses with DNMT3a in DRG neurons, CREB may be a key player in CIPNP through transcriptional activation of the Dnmt3a gene in primary sensory neurons. CREB is thus a likely potential target for the therapeutic management of this disorder.
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Emerging evidence suggests mild traumatic brain injury related headache (MTBI-HA) is a form of neuropathic pain state. Previous supraspinal mechanistic studies indicate patients with MTBI-HA demonstrate a dissociative state with diminished levels of supraspinal prefrontal pain modulatory functions and enhanced supraspinal sensory response to pain in comparison to healthy controls. However, the relationship between supraspinal pain modulatory functional deficit and severity of MTBI-HA is largely unknown. ⋯ In the moderate-headache group, a significant (T = -3.05, p < 0.01) decrease in resting state activity was observed in the left superior parietal cortex when compared to the mild-headache group. In the severe-headache group, significant decreases in resting state supraspinal activities in the right insula (T = -3.46, p < 0.001), right premotor cortex (T = -3.30, p < 0.01), left premotor cortex (T = -3.84, p < 0.001), and left parietal cortex (T = -3.94, p < 0.0001), and an increase in activity in the right secondary somatosensory cortex (T = 4.05, p < 0.0001) were observed when compared to the moderate-headache group. The results of the study suggest that the increase in MTBI-HA severity may be associated with an imbalance in the supraspinal pain network with decline in supraspinal pain modulatory function and enhancement of sensory/pain decoding.
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Cortical long-term potentiation (LTP) serves as a cellular model for chronic pain. As an important subtype of adenylyl cyclases (ACs), adenylyl cyclase subtype 1 (AC1) is critical for the induction of cortical LTP in the anterior cingulate cortex (ACC). Genetic deletion of AC1 or pharmacological inhibition of AC1 blocked behavioral allodynia in animal models of neuropathic and inflammatory pain. ⋯ Genetic deletion of AC1 also reduced allodynia responses in models of neuropathic pain and chronic inflammation pain in adult female mice. In brain slices of adult female mice, bath application of NB001(20 μM) blocked the induction of LTP in ACC. Our results indicate that calcium-stimulated AC1 is required for injury-related cortical LTP and behavioral allodynia in both sexes of adult animals, and NB001 can be used as a potential therapeutic drug for treating neuropathic and inflammatory pain in man and woman.
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This study aimed to explore the application value of nalbuphine in pulsed radiofrequency operation of trigeminal ganglion in patients with postherpetic neuralgia (PHN). Thirty patients with PHN were randomly divided into the nalbuphine (Nalbu) group and ketorolac tromethamine (KT) group and received CT-guided pulsed radiofrequency surgery on trigeminal ganglion. The numeric rating scale (NRS) scores of patients were recorded at preoperative, intraoperative, and postoperative time points, before going to bed, and the next morning after the operation. ⋯ The outcome data demonstrated that patients treated with nalbuphine had lower NRS scores after the pulse radiofrequency operation during and after the pulse radiofrequency operation compared to those with KT. In addition, nalbuphine effectively decreased the number of breakthrough pain, reduced the occurrence of nausea and vomiting after surgery, and improved the sleep quality. In conclusion, intramuscular injection of nalbuphine 30 min before trigeminal ganglion pulse radiofrequency surgery can be conducive to pain relief and improve the postoperative comfort of patients, providing an effective alternative for the alleviation of PHN in clinic.