Drug Management of Visceral Pain: Concepts from Basic Research

Visceral pain is experienced by 40% of the population, and 28% of cancer patients suffer from pain arising from intra- abdominal metastasis or from treatment. Neuroanatomy of visceral nociception and neurotransmitters, receptors, and ion channels that modulate visceral pain are qualitatively or quantitatively different from those that modulate somatic and neuropathic pain. Visceral pain should be recognized as distinct pain phenotype. TRPV1, Na 1.8, and ASIC3 ion channels and peripheral kappa opioid receptors are important mediators of visceral pain. Mu agonists, gabapentinoids, and GABAB agonists reduce pain by binding to central receptors and channels. Combinations of analgesics and adjuvants in animal models have supra-additive antinociception and should be considered in clinical trials. This paper will discuss the neuroanatomy, receptors, ion channels, and neurotransmitters important to visceral pain and provide a basic science rationale for analgesic trials and management

Recent advances in the treatment of pain

Cancer pain and chronic non-malignant pain can be difficult to manage and may not respond satisfactorily to standard analgesics. Sequential empiric analgesic trials are usually done to manage individual patients. Experimental human pain models have helped to clarify mechanisms of opioid and adjuvant analgesic actions. Combinations of opioids and adjuvant analgesics better relieve pain than either opioids or adjuvant analgesics alone, as demonstrated in randomized controlled trials. The analgesic activity of antidepressants is largely dependent upon norepinephrine reuptake and activation of alpha 2 adrenergic receptors. Corticosteroids reduce postoperative orthopedic incident pain, which may allow patients to ambulate earlier and with less pain. Spinal corticosteroids reduce lower hemibody pain. Gabapentinoids as single high doses reduce postoperative pain and certain acute pain syndromes. Individuals who experience flares of pain while on spinal opioids benefit from intrathecal boluses of levobupivicaine or sublingual ketamine. Interventional approaches to pain management are often necessary due to the limitations of systemic analgesics. Electronics stimulators (peripheral, spinal and motor cortex) improve difficult to manage chronic pain syndromes. Pulsed radiofrequency reduces pain without tissue damage, which could be an advantage over chemical or radiofrequency neurotomy. Botulinum toxin A reduces focal neuropathic pain that is durable. Interventional related successes in relieving pain are operator dependent. Most reported benefits of systemic and regional analgesics and interventional approaches to pain relief are not based on randomized trials and are subject to selection bias, sampling error, and placebo responses, which may over-inflate reported benefits. Randomized controlled trials are needed to confirm reported benefits

Interpretable Subgroup Discovery in Treatment Effect Estimation with Application to Opioid Prescribing Guidelines

The dearth of prescribing guidelines for physicians is one key driver of the current opioid epidemic in the United States. In this work, we analyze medical and pharmaceutical claims data to draw insights on characteristics of patients who are more prone to adverse outcomes after an initial synthetic opioid prescription. Toward this end, we propose a generative model that allows discovery from observational data of subgroups that demonstrate an enhanced or diminished causal effect due to treatment. Our approach models these sub-populations as a mixture distribution, using sparsity to enhance interpretability, while jointly learning nonlinear predictors of the potential outcomes to better adjust for confounding. The approach leads to human-interpretable insights on discovered subgroups, improving the practical utility for decision suppor

Phase II evaluation of piroxantrone in renal cell carcinoma

The Southwest Oncology Group (SWOG) studied the response rate and toxicity of piroxantrone (150 mg/m 2 q 21 days) in patients with advanced metastatic renal cell carcinoma. Among 32 eligible patients, there were no partial nor complete responses. There were two mixed responses. Significant white cell toxicity, anemia, nausea, and vomiting were observed. Mild or moderate degrees of fever, malaise, and stomatitis occurred. No significant cardiac toxicity was noted. Piroxantrone does not have significant activity as a single agent in advanced renal cell carcinoma.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45142/1/10637_2004_Article_BF00873131.pd