Mol Pain
-
Pain is a serious clinical challenge, and is associated with a significant reduction in quality of life and high financial costs for affected patients. Research efforts have been made to explore the etiological basis of pain to guide the future treatment of patients suffering from pain conditions. ⋯ In the present review, we summarized major findings in recent studies which examined the roles of KA receptor dysregulation in nociceptive transmission and in pain. This timely overview of current knowledge will help to provide a framework for future developing novel therapeutic strategies to manage pain.
-
Recent reports suggest pain from surgical injury may influence the risks associated with exposure to opioids. In mice, hind-paw incision attenuates morphine-primed reinstatement due to kappa opioid receptor activation by dynorphin. In this focused group of studies, we examined the hypotheses that kappa-opioid receptor activation in the nucleus accumbens mediates attenuated drug- primed reinstatement after incisional surgery, and the G-protein biased mu-opioid agonist, oliceridine, leads to less priming of the dynorphin effect in comparison to morphine. ⋯ Persistently elevated levels of prodynorphin expression in the medial prefrontal cortex and nucleus accumbens were observed in the incised morphine-treated animals. However, both behavioral and molecular changes were absent in animals with incisional injury conditioned with oliceridine. These findings suggest a role for prodynorphin expression in the nucleus accumbens with exposure to morphine after surgery that may protect individuals from relapse not shared with biased mu- opioid receptor agonists.
-
Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer's disease. Chronic pain is experienced by the vast majority of patients living with Parkinson's disease. The degeneration of dopaminergic neuron acts as the essential mechanism of Parkinson's disease in the midbrain dopaminergic pathway. ⋯ Key cortical areas, such as the anterior cingulate cortex (ACC) and insular cortex (IC) that receive the dopaminergic projections are involved in pain transmission. Dopamine changes synaptic transmission via several pathway, for example the D2-adenly cyclase (AC)-cyclic AMP (cAMP)-protein kinase A (PKA) pathway and D1-G protein-coupled receptor kinase 2 (GRK2)-fragile X mental retardation protein (FMRP) pathway. The management of Parkinson's disease-related pain implicates maintenance of stable level of dopaminergic drugs and analgesics, however a more selective drug targeting at key molecules in Parkinson's disease-related pain remains to be investigated.
-
Chronic low back pain (CLBP) is often treated with opioid analgesics (OA), a class of medications associated with a significant risk of misuse. However, little is known about how treatment with OA affect the brain in chronic pain patients. Gaining this knowledge is a necessary first step towards understanding OA associated analgesia and elucidating long-term risk of OA misuse. ⋯ CLBP patients medicated with OA showed loss of volume in the nucleus accumbens and thalamus, and an overall significant decrease in signal to noise ratio in their sub-cortical areas. Power spectral density analysis (PSD) of frequency content in the accumbens' resting state activity revealed that both medicated and unmedicated patients showed loss of PSD within the slow-5 frequency band (0.01-0.027 Hz) while only CLBP patients on OA showed additional density loss within the slow-4 frequency band (0.027-0.073 Hz). We conclude that chronic treatment with OA is associated with altered brain structure and function within sensory limbic areas.
-
Neuropathic pain following peripheral nerve injury (PNI) is linked to neuroinflammation in the spinal cord marked by astrocyte activation and upregulation of interleukin 6 (IL-6), chemokine (C-C motif) ligand 2 (CCL2) and chemokine (C-X-C motif) ligand 1 (CXCL1), with inhibition of each individually being beneficial in pain models. ⋯ SUR1-TRPM4 may represent a novel non-addicting target for neuropathic pain.