The journal of pain : official journal of the American Pain Society
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Breast cancer metastasizes to bone, diminishing quality of life of patients because of pain, fracture, and limited mobility. Cancer-induced bone pain (CIBP) is characterized as moderate to severe ongoing pain, primarily managed by mu opioid agonists such as fentanyl. However, opioids are limited by escalating doses and serious side effects. ⋯ U50,488 blocked this pain without altering tumor-induced bone loss or tumor growth. Follow-up studies in human cancer cell lines confirmed that KOR agonists do not affect cancer cell proliferation. These studies suggest that KOR agonists could be a new target for cancer pain management that does not induce cancer cell proliferation or alter bone loss.
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Chronic pain is a major public health concern, and widespread use of prescription opioids for chronic pain has contributed to the escalating problem of opioid use disorder. Interdisciplinary pain rehabilitation programs (IPRPs) can be highly effective in discontinuing opioids in patients with chronic pain while also improving functional status. This study sought to examine self-report and performance-based functional outcomes of 2 cohorts of patients enrolled in a 3-week IPRP: patients engaged in interdisciplinary pain treatment and physician-supervised opioid taper versus nonopioid users engaged in interdisciplinary treatment. ⋯ Group × Period interactions were nonsignificant whereas period effects were significant for all outcomes in directions indicating improvement (Ps < .001) at discharge from the program and at 6 months, irrespective of opioid use status. Results support the assertion that IPRPs lead to significant improvements in subjective as well as objective indices of function, irrespective of opioid use status. Implications for our findings are discussed.
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Cognitive biases that emphasize bodily harm, injury, and illness could play a role in the maintenance of chronic pain by facilitating fear and avoidance. Whereas extensive research has established attention, interpretation, and memory biases in adults with chronic pain, far less is known about these same biases in children and adolescents with pain. Studying cognitive biases in attention, interpretation, and memory in relation to pain occurring in youth is important because youth is a time when pain can first become chronic, and when relationships between cognitive biases and pain outcomes emerge and stabilize. ⋯ In this article, we summarize the growing corpus of data that have measured cognitive biases in relation to pediatric pain. We conclude that although biases in attention, interpretation, and memory characterize children and adolescents with varying pain experiences, questions regarding the direction, magnitude, nature, and role of these biases remain. We call for independent extension of cognitive bias research in children and adolescents, using well powered longitudinal studies with wide age ranges and psychometrically sound experimental measures to clarify these findings and any developmental trends in the links between cognitive biases and pain outcomes.
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Increased HCN Channel Activity in the Gasserian Ganglion Contributes to Trigeminal Neuropathic Pain.
Orofacial neuropathic pain caused by trigeminal nerve injury is a debilitating condition with limited therapeutic options. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels regulate neuronal excitability and are involved in the development and maintenance of chronic pain. However, the effect of HCN channel activity in the Gasserian ganglion on trigeminal neuropathic pain has not been examined. We evaluated nociceptive behaviors after microinjection of the HCN channel blockers ZD7288 or ivabradine into the Gasserian ganglion in rats with trigeminal nerve injury. Both blockers dose-dependently ameliorated evoked and spontaneous nociceptive behavior in rats with trigeminal neuropathic pain. Moreover, the clinically available HCN channel blocker ivabradine showed a prolonged antinociceptive effect. In the Gasserian ganglion, HCN1 and HCN2 are major HCN isoforms. After trigeminal nerve injury, the counts of HCN1 as well as HCN2 immuno-positive punctae were increased in the ipsilateral Gasserian ganglions. These results indicate that the increased HCN channel activity in the Gasserian ganglion directly contributes to neuropathic pain resulting from trigeminal nerve injury. ⋯ Trigeminal nerve damage-induced orofacial pain is severe and more resistant to standard pharmacological treatment than other types of neuropathic pain. Our study suggests that targeting HCN channel activities in the Gasserian ganglion may provide an alternative treatment of trigeminal neuropathy including trigeminal neuralgia.
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In recent years, the disappointing history of translation in pain research has undergone significant scrutiny. The escalation of knowledge and understanding related to presumed pain in neuropathic and inflammatory animal models contrasted with the unsatisfactory record of "bench-to-bedside" translation has raised many questions about the validity and clinical relevance of preclinical models and methods of behavioral assessment. Although many opinions have been expressed one of the overriding concerns and greatest barriers to the widening gap between preclinical research and the development of new interventions has been the underappreciated distinction between pain and nociception. ⋯ Other issues important to the discussion include but are not limited to the predictive validity of preclinical models, and the neglect of gender, age, and comorbidities in the design of preclinical studies. On the clinical side, the lack of sanitization of phenotypes in clinical trials has also contributed to the insufficient success of efforts to translate basic research to the clinic. The current review will discuss these and other issues believed to have contributed to the existing obstacles and challenges facing pain research along with making recommendations for the future.