Injectable Capsaicin for the Management of Pain Due to Osteoarthritis.

Capsaicin is a potent agonist of the TRPV1 channel, a transduction channel that is highly expressed in nociceptive fibers (pain fibers) throughout the peripheral nervous system. Given the importance of TRPV1 as one of several transduction channels in nociceptive fibers, much research has been focused on the potential therapeutic benefits of using TRPV1 antagonists for the management of pain. However, an antagonist has two limitations.

Fight fire with fire: Neurobiology of capsaicin-induced analgesia for chronic pain.

Capsaicin, the pungent ingredient in chili peppers, produces intense burning pain in humans. Capsaicin selectively activates the transient receptor potential vanilloid 1 (TRPV1), which is enriched in nociceptive primary afferents, and underpins the mechanism for capsaicin-induced burning pain. Paradoxically, capsaicin has long been used as an analgesic.

John J. Bonica Award Lecture: Peripheral neuronal hyperexcitability: the "low-hanging" target for safe therapeutic strategies in neuropathic pain.

Neuropathic pain (NP) resulting from injury or disease of the somatosensory system is a common, debilitating chronic disorder that significantly undermines quality of life. Preclinical and clinical studies have considerably advanced our understanding of the myriad peripheral and central changes in neuronal and non-neuronal cells associated with persistent pain states. Disappointingly, advances in clinical therapies for NP have not paralleled the substantial advances in basic science.

Improving Study Conduct and Data Quality in Clinical Trials of Chronic Pain Treatments: IMMPACT Recommendations.

The estimated probability of progressing from phase 3 analgesic clinical trials to regulatory approval is approximately 57%, suggesting that a considerable number of treatments with phase 2 trial results deemed sufficiently successful to progress to phase 3 do not yield positive phase 3 results. Deficiencies in the quality of clinical trial conduct could account for some of this failure. An Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials meeting was convened to identify potential areas for improvement in trial conduct in order to improve assay sensitivity (ie, ability of trials to detect a true treatment effect).

Randomized, Double-Blind, Placebo-Controlled Trial of Intraarticular Trans-Capsaicin for Pain Associated With Osteoarthritis of the Knee.

Objective: To assess the efficacy and safety of high-purity synthetic trans-capsaicin (CNTX-4975) in patients with chronic moderate-to-severe osteoarthritis (OA)-associated knee pain.

Methods: In this phase II multicenter double-blind study, patients ages 45-80 years who had stable knee OA were randomized in a 2:1:2 ratio to receive a single intraarticular injection of placebo, CNTX-4975 0.5 mg, or CNTX-4975 1.

Ca and calpain mediate capsaicin-induced ablation of axonal terminals expressing transient receptor potential vanilloid 1.

Capsaicin is an ingredient in spicy peppers that produces burning pain by activating transient receptor potential vanilloid 1 (TRPV1), a Ca-permeable ion channel in nociceptors. Capsaicin has also been used as an analgesic, and its topical administration is approved for the treatment of certain pain conditions. The mechanisms underlying capsaicin-induced analgesia likely involve reversible ablation of nociceptor terminals.

Use of Capsaicin to Treat Pain: Mechanistic and Therapeutic Considerations.

Capsaicin is the pungent ingredient of chili peppers and is approved as a topical treatment of neuropathic pain. The analgesia lasts for several months after a single treatment. Capsaicin selectively activates TRPV1, a Ca-permeable cationic ion channel that is enriched in the terminals of certain nociceptors.

A randomized, double-blind, placebo-controlled trial of injected capsaicin for pain in Morton's neuroma.

Intermetatarsal neuroma or Morton's neuroma is a painful condition of the foot resulting from an entrapment of the common digital nerve typically in the third intermetatarsal space. The pain can be severe and especially problematic with walking. Treatment options are limited and surgery may lead to permanent numbness in the toes.

individual variation in sleep quality and duration is related to cerebral mu opioid receptor binding potential during tonic laboratory pain in healthy subjects.

Objective: Although poor sleep is a consequence of pain, sleep disturbance reciprocally induces hyperalgesia and exacerbates clinical pain. Conceptual models of chronic pain implicate dysfunctional supraspinal pain processing mechanisms, mediated in part by endogenous opioid peptides. Our preliminary work indicates that sleep disruption impairs psychophysical measures of descending pain modulation, but few studies have investigated whether insufficient sleep may be associated with alterations in endogenous opioid systems.

Randomized control trial of topical clonidine for treatment of painful diabetic neuropathy.

A length-dependent neuropathy with pain in the feet is a common complication of diabetes (painful diabetic neuropathy). It was hypothesized that pain may arise from sensitized-hyperactive cutaneous nociceptors, and that this abnormal signaling may be reduced by topical administration of the α(2)-adrenergic agonist, clonidine, to the painful area. This was a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial.

Pain sensitivity and vasopressin analgesia are mediated by a gene-sex-environment interaction.

Quantitative trait locus mapping of chemical/inflammatory pain in the mouse identified the Avpr1a gene, which encodes the vasopressin-1A receptor (V1AR), as being responsible for strain-dependent pain sensitivity to formalin and capsaicin. A genetic association study in humans revealed the influence of a single nucleotide polymorphism (rs10877969) in AVPR1A on capsaicin pain levels, but only in male subjects reporting stress at the time of testing. The analgesic efficacy of the vasopressin analog desmopressin revealed a similar interaction between the drug and acute stress, as desmopressin inhibition of capsaicin pain was only observed in nonstressed subjects.

A new program in pain medicine for medical students: integrating core curriculum knowledge with emotional and reflective development.

Objective: Improvements in clinical pain care have not matched advances in scientific knowledge, and innovations in medical education are needed. Several streams of evidence indicate that pain education needs to address both the affective and cognitive dimensions of pain. Our aim was to design and deliver a new course in pain establishing foundation-level knowledge while comprehensively addressing the emotional development needs in this area.

Self-reported sleep duration associated with distraction analgesia, hyperemia, and secondary hyperalgesia in the heat-capsaicin nociceptive model.

Although sleep deprivation is known to heighten pain sensitivity, the mechanisms by which sleep modifies nociception are largely unknown. Few studies of sleep-pain interactions have utilized quantitative sensory testing models that implicate specific underlying physiologic mechanisms. One possibility, which is beginning to receive attention, is that differences in sleep may alter the analgesic effects of distraction.

Obturator nerve transfer as an option for femoral nerve repair: case report.

Objective: Nerve transfers have proved to be an important addition to the armamentarium in the repair of brachial plexus lesions, but have been used sparingly for lower extremity nerve repair. Here, we present what is believed to be the first description of a successful transfer of the obturator nerve to the femoral nerve.

Clinical Presentation: A 45-year-old woman presented with a complete femoral nerve lesion after removal of a large (15-cm) schwannoma of the retroperitoneum involving the lumbar plexus.

Catastrophizing delays the analgesic effect of distraction.

Behavioral analgesic techniques such as distraction reduce pain in both clinical and experimental settings. Individuals differ in the magnitude of distraction-induced analgesia, and additional study is needed to identify the factors that influence the pain relieving effects of distraction. Catastrophizing, a set of negative emotional and cognitive processes, is widely recognized to be associated with increased reports of pain.

Conduction properties distinguish unmyelinated sympathetic efferent fibers and unmyelinated primary afferent fibers in the monkey.

Background: Different classes of unmyelinated nerve fibers appear to exhibit distinct conductive properties. We sought a criterion based on conduction properties for distinguishing sympathetic efferents and unmyelinated, primary afferents in peripheral nerves.

Methodology/principal Findings: In anesthetized monkey, centrifugal or centripetal recordings were made from single unmyelinated nerve fibers in the peroneal or sural nerve, and electrical stimuli were applied to either the sciatic nerve or the cutaneous nerve endings, respectively.

Polymorphisms in the GTP cyclohydrolase gene (GCH1) are associated with ratings of capsaicin pain.

Though it is clear that genomic variability plays an integral role in accounting for pain sensitivity, controversy exists over which genes are involved. While recent data suggest a "protective" (i.e.

Mechanisms of neuropathic pain.

Neuropathic pain refers to pain that originates from pathology of the nervous system. Diabetes, infection (herpes zoster), nerve compression, nerve trauma, "channelopathies," and autoimmune disease are examples of diseases that may cause neuropathic pain. The development of both animal models and newer pharmacological strategies has led to an explosion of interest in the underlying mechanisms.

Surgical treatment of thoracic outlet syndrome: a randomized trial comparing two operations.

Object: Various surgical approaches have been proposed for the treatment of thoracic outlet syndrome (TOS). The authors of this study focused on the differences in outcome after supraclavicular neuroplasty of brachial plexus (SNBP [no rib resection]) and transaxillary first rib resection (TFRR) in patients in whom the dominant clinical problem was pain.

Methods: Fifty-five patients were randomized to undergo TFRR or SNBP.

Vertebral synovial chondromatosis. Report of two cases and review of the literature.

Synovial chondromatosis is an uncommon disorder characterized by the formation of multiple cartilaginous nodules within the synovium, most commonly affecting large joints. Its involvement with the spine is rare; only six cases have been reported. The authors describe two patients with synovial chondromatosis involving the cervical spine.

Vulnerability of the subcostal nerve to injury during bone graft harvesting from the iliac crest.

Object: Autologous bone graft harvesting from the iliac crest remains the gold standard for fusion surgery. One disadvantage of autologous bone harvesting is the patient's enduring postoperative pain at the donor site. Nerve injury is one of the postulated mechanisms that may account for this pain.