Pain
-
Classical trigeminal neuralgia (TN) is a severe neuropathic facial pain disorder commonly associated with neurovascular compression at the trigeminal nerve root entry zone (REZ). Neurosurgical interventions can relieve TN pain, but the mechanisms underlying these effects are unknown. We determined whether the abnormalities we previously reported at the REZ of TN patients using diffusion tensor imaging (DTI) and brain gray matter (GM) analyses resolve after effective neurosurgical treatment. ⋯ At the REZ, effective treatment reversed FA, MD, RD, and AD abnormalities and was correlated with pain relief after treatment. These results demonstrate that treatment can effectively resolve pain by normalizing REZ abnormalities, which may influence vAI abnormalities. Future studies should consider DTI as an adjunct to assess the patient outcome and subtle microstructural changes after treatment.
-
Intense inflammatory pain caused by urate crystals in joints and other tissues is a major symptom of gout. Among therapy drugs that lower urate, benzbromarone (BBR), an inhibitor of urate transporters, is widely used because it is well tolerated and highly effective. We demonstrate that BBR is also an activator of voltage-gated KCNQ potassium channels. ⋯ Notably, the analgesic effects of BBR are largely mediated through peripheral and not through central KCNQ channels, an observation supported both by pharmacokinetic studies and in vivo experiments. Moreover, multiple residues in the superficial part of the voltage sensing domain of KCNQ channels were identified critical for the potentiation activity of BBR by a molecular determinant investigation. Our data indicate that activation of peripheral KCNQ channels mediates the pain relief effects of BBR, potentially providing a new strategy for the development of more effective therapies for gout.
-
Primary hyperalgesia is characterized by increased responsiveness to both heat and mechanical stimulation in the area of injury. By contrast, secondary hyperalgesia is generally associated with increased responses to mechanical but not heat stimuli. We tested the hypothesis that sensitization in secondary hyperalgesia is dependent on the class of peripheral nociceptor (C- or A-nociceptor) rather than the modality of stimulation (mechanical vs heat). ⋯ Neurons in the superficial dorsal horn receive and process nociceptor inputs from the area of primary hyperalgesia, resulting in functional sensitization to C-nociceptive inputs. In inflammatory arthritis, secondary hyperalgesia is evoked by A-nociceptor thermal stimulation, suggesting that secondary hyperalgesia is A-nociceptor, rather than stimulus modality (mechanical vs thermal), dependent. Fos-like immunoreactivity evoked by A-nociceptor stimulation in secondary hyperalgesia suggests that the sensitization is underpinned by spinal neuronal sensitization in laminae I and IV/V.