Pain
-
Itch is a protective sensation producing a desire to scratch. Pathologic itch can be a chronic symptom of illnesses such as uremia, cholestatic liver disease, neuropathies and dermatitis, however current therapeutic options are limited. Many types of cell surface receptors, including those present on cells in the skin, on sensory neurons and on neurons in the spinal cord, have been implicated in itch signaling. ⋯ The pruriceptive defect in R7bp knockout mice was rescued in double knockout mice also lacking Oprk1, encoding the G protein-coupled kappa-opioid receptor whose activation is known to inhibit itch sensation. In a model of atopic dermatitis (eczema), R7bp knockout mice showed diminished scratching behavior and enhanced sensitivity to kappa opioid agonists. Taken together, our results indicate that R7bp is a key regulator of itch sensation and suggest the potential targeting of R7bp-dependent GTPase activating protein activity as a novel therapeutic strategy for pathological itch.
-
Erythromelalgia (EM) is a rare neurovascular disorder characterized by intermittent severe burning pain, erythema, and warmth in the extremities on heat stimuli. To investigate the underlying pathophysiology, peripheral axonal excitability studies were performed and changes with heating and therapy explored. Multiple excitability indices (stimulus-response curve, strength-duration time constant (SDTC), threshold electrotonus, and recovery cycle) were investigated in 23 (9 EMSCN9A+ and 14 EMSCN9A-) genetically characterized patients with EM stimulating median motor and sensory axons at the wrist. ⋯ Taken together, these changes may be attributed to systemic neurovascular abnormalities in EM, with chronic postischaemic resting membrane potential hyperpolarization due to Na/K pump overactivity. With heating, a trigger of acute symptoms, axonal depolarization developed, corresponding to acute axonal ischaemia. This study has provided novel insights into EM pathophysiology.
-
The aim of this study was to identify clinical risk factors for unfavorable pain trajectories after breast cancer surgery, to better understand the association between pain expectation, psychological distress, and acute postoperative pain. This prospective study included 563 women treated for breast cancer. Psychological data included questionnaires for depressive symptoms and anxiety. ⋯ The results confirm that acute pain after breast cancer surgery is a multidimensional phenomenon. Psychological distress, pain expectation, and the patients' report of preoperative pain in the area to be operated should be recognized before surgery. Patients having axillary clearance need more efficient analgesic approaches.
-
Bone cancer pain has been reported to have unique mechanisms and is resistant to morphine treatment. Recent studies have indicated that neuron-restrictive silencer factor (NRSF) plays a crucial role in modulating the expression of the μ-opioid receptor (MOR) gene. The present study elucidates the regulatory mechanisms of MOR and its ability to affect bone cancer pain. ⋯ Furthermore, genetically knocking down NRSF with antisense oligodeoxynucleotide rescued the expression of MOR and potentiated the systemic morphine analgesia. The present results suggest that in sarcoma-induced bone cancer pain, NRSF-induced downregulation of MOR is involved in the reduction of morphine analgesia. Epigenetically, up-regulation of MOR could substantially improve the effect of system delivery of morphine.