Articles: neuropathic-pain.
-
Brain Behav. Immun. · Oct 2014
Neuropathic pain-induced depressive-like behavior and hippocampal neurogenesis and plasticity are dependent on TNFR1 signaling.
Patients suffering from neuropathic pain have a higher incidence of mood disorders such as depression. Increased expression of tumor necrosis factor (TNF) has been reported in neuropathic pain and depressive-like conditions and most of the pro-inflammatory effects of TNF are mediated by the TNF receptor 1 (TNFR1). Here we sought to investigate: (1) the occurrence of depressive-like behavior in chronic neuropathic pain and the associated forms of hippocampal plasticity, and (2) the involvement of TNFR1-mediated TNF signaling as a possible regulator of such events. ⋯ The onset of depressive-like behavior also coincided with increased hippocampal levels of TNF, and decreased expression of TNF receptor 2 (TNFR2), which were all fully restored after mice spontaneously recovered from pain. Notably, TNFR1(-/-) mice did not develop depressive-like symptoms after injury, nor were there changes in hippocampal neurogenesis and plasticity. Our data show that neuropathic pain induces a cluster of depressive-like symptoms and profound hippocampal plasticity that are dependent on TNF signaling through TNFR1.
-
Painful diabetic neuropathy is a disease of the peripheral sensory neuron with impaired opioid responsiveness. Since μ-opioid receptor (MOR) activation can inhibit the transient receptor potential vanilloid 1 (TRPV1) activity in peripherally sensory neurons, this study investigated the mechanisms of impaired opioid inhibitory effects on capsaicin-induced TRPV1 activity in painful diabetic neuropathy. Intravenous injection of streptozotocin (STZ, 45 mg/kg) in Wistar rats led to a degeneration of insulin producing pancreatic β-cells, elevated blood glucose, and mechanical hypersensitivity (allodynia). ⋯ Intrathecal delivery of nerve growth factor in diabetic animals normalized sensory neuron MOR and subsequently rescued morphine's inhibitory effects on capsaicin-induced TRPV1 activity in vivo and in vitro. These findings identify a loss in functional MOR on sensory neurons as a contributing factor for the impaired opioid inhibitory effects on capsaicin-induced TRPV1 activity during advanced STZ-induced diabetes. Moreover, they support growing evidence of a distinct regulation of opioid responsiveness during various painful states of disease (e.g. arthritis, cancer, neuropathy) and may give novel therapeutic incentives.
-
Long-term potentiation of glutamatergic transmission has been observed after physiological learning or pathological injuries in different brain regions, including the spinal cord, hippocampus, amygdala, and cortices. The insular cortex is a key cortical region that plays important roles in aversive learning and neuropathic pain. However, little is known about whether excitatory transmission in the insular cortex undergoes plastic changes after peripheral nerve injury. ⋯ Genetic deletion of adenylyl cyclase subtype 1 (AC1) prevented the translocation of AKAP79/150 and PKA, as well as the upregulation of synaptic GluA1-containing AMPARs. Pharmacological inhibition of calcium-permeable AMPAR function in the insular cortex reduced behavioral sensitization caused by nerve injury. Our results suggest that the expression of AMPARs is enhanced in the insular cortex after nerve injury by a pathway involving AC1, AKAP79/150, and PKA, and such enhancement may at least in part contribute to behavioral sensitization together with other cortical regions, such as the anterior cingulate and the prefrontal cortices.
-
Complex craniofacial pain can be a challenging condition to manage both medically and surgically, but there is a resurgence of interest in the role of neurostimulation therapy. Surgical options for complex craniofacial pain syndromes include peripheral nerve/field stimulation, ganglion stimulation, spinal cord stimulation, dorsal nerve root entry zone lesioning, motor cortex stimulation, and deep brain stimulation. Peripheral nerve/field stimulation is rapidly being explored and is preferred by both patients and surgeons. Technological advances and improved understanding of the interactions of pain pathways with its affective component will widen the scope of neurostimulation therapy for craniofacial pain syndromes.
-
Recent studies have revealed the antinociceptive effects of glycine transporter (GlyT) inhibitors in neuropathic pain models such as sciatic nerve-injured and diabetic animals. Bone cancer can cause the most severe pain according to complex mechanisms in which a neuropathic element is included. Bone cancer modifies the analgesic action of opioids and limits their effectiveness, and thus novel medicament for bone cancer pain is desired. ⋯ GlyT inhibitors with or without morphine may be a new strategy for the treatment of bone cancer pain and lead to further investigations of the mechanisms underlying the development of bone cancer pain.