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Fatty-acid amide hydrolase (FAAH) is an intracellular serine hydrolase that catalyzes the cleavage of endogenous fatty-acid amides, including the endocannabinoid anandamide (AEA). We previously reported that the peripherally restricted FAAH inhibitor URB937, which selectively increases AEA levels outside the central nervous system, reduces hyperalgesia and c-Fos expression in the trigeminal nucleus caudalis (TNC) and the locus coeruleus in an animal model of migraine based on nitroglycerin (NTG) administration.
Learn More >Pharmacological treatment of patients with tension-type headache (TTH) includes symptomatic (acute) and prophylactic (preventive) medication. No previous study has investigated variables associated to symptomatic medication intake in TTH. Our aim was to assess the association of clinical, psychological and neurophysiological outcomes with the use and timing of the use of symptomatic medication in TTH.
Learn More >Stress and pain have been interrelated in clinical widespread pain conditions. Studies indicate that acute experimental stress in healthy volunteers has a negative effect on the descending inhibitory pain control system and thus the ability to inhibit one painful stimulus with another (conditioned pain modulation [CPM]) although without effect on general pain sensitivity. CPM effects can be assessed immediately after the stress induction, whereas some physiological stress responses (e.g., cortisol release) are delayed and longer lasting. It is unclear whether CPM may relate to stress-induced increases in cortisol.
Learn More >Societal costs of low back pain are high, yet few studies have been performed to identify predictive factors of high societal costs among chronic low back pain patients. This study aimed to determine which factors predict high societal costs in patients with chronic low back pain.
Learn More >The objective of the present analysis was to determine whether changes in Brief Pain Inventory (BPI) average pain by patient global impression of improvement (PGI-I) category and the cut-off for clinically important difference (CID) were different between Asian and Caucasian patients with chronic pain due to osteoarthritis. This analysis used data from 3 (Caucasian) and 2 (Asian) randomized, placebo-controlled, 10- to 14-week duloxetine studies for the treatment of patients aged ≥40 years with osteoarthritis pain. The receiver operating characteristic (ROC) analysis was used to characterize the association between changes in BPI average pain and PGI-I levels at study endpoint. The CID was characterized by PGI-I and the cut-off point for CID in BPI average pain was determined by the intersection of a 45̊ tangent line with each ROC curve. Data from 668 Asian and 868 Caucasian patients were available for analysis. Baseline BPI average pain ratings including worst and least pain were comparable between Asians and Caucasians. Ratings for percentage change from baseline to endpoint for BPI average pain in Asian patients and Caucasian patients were similar across the 7 PGI-I categories, regardless of age, gender, study, and treatment. The ROC analysis results of cut-off points in BPI average pain demonstrated the raw change cut-off was -3.0, and percentage change cut-off was -40% for both Asian and Caucasian patients. Overall, the present analysis concludes changes in BPI average pain by PGI-I category and the cut-off for CID were similar for Asian and Caucasian patients with chronic pain due to osteoarthritis.
Learn More >Spasticity and pain frequently co-occur in persons with spinal cord injury (SCI), yet, how these sequelae interact in daily life is unclear. Additionally, little is known about how psychological factors relate to the perception of spasticity and its impacts on daily life.
Learn More >Paclitaxel (Brand name Taxol) is widely used in the treatment of common cancers like breast, ovarian and lung cancer. Although highly effective in blocking tumor progression, paclitaxel also causes peripheral neuropathy as a side effect in 60-70% of chemotherapy patients. Recent efforts by numerous labs have aimed at defining the underlying mechanisms of paclitaxel-induced peripheral neuropathy (PIPN). In vitro models using rodent dorsal root ganglion neurons, human induced pluripotent stem cells, and rodent in vivo models have revealed a number of molecular pathways affected by paclitaxel within axons of sensory neurons and within other cell types, such as the immune system and peripheral glia, as well skin. These studies revealed that paclitaxel induces altered calcium signaling, neuropeptide and growth factor release, mitochondrial damage and reactive oxygen species formation, and can activate ion channels that mediate responses to extracellular cues. Recent studies also suggest a role for the matrix-metalloproteinase 13 (MMP-13) in mediating neuropathy. These diverse changes may be secondary to paclitaxel-induced microtubule transport impairment. Human genetic studies, although still limited, also highlight the involvement of cytoskeletal changes in PIPN. Newly identified molecular targets resulting from these studies could provide the basis for the development of therapies with which to either prevent or reverse paclitaxel-induced peripheral neuropathy in chemotherapy patients.
Learn More >This updated systematic review evaluated the efficacy, acceptability and safety of long-term opioid therapy (LTOT) for chronic non-cancer pain (CNCP).
Learn More >Atopic dermatitis (AD) is a highly pruritic chronic inflammatory skin disorder. Ruxolitinib, a selective inhibitor of Janus kinase (JAK)-1 and JAK2, potently suppresses cytokine signaling involved in AD pathogenesis.
Learn More >: The use of ketamine infusions for chronic pain has surged, with utilization exceeding the proliferation of knowledge. A proposed mechanism for the long-term benefit in chronic pain is that ketamine may alter the affective-motivational component of pain.: In this review, we discuss the classification and various dimensions of pain, and explore the effects of ketamine on different pain categories and components. The relationship between ketamine's action at the NMDA receptor, the development of chronic pain, and the its possible role in preventing the persistence of pain are examined. We also summarize animal models evaluating the antinociceptive effects of ketamine and risk mitigation strategies of ketamine-associated side effects.: Although ketamine exerts most of its analgesic effects via the NMDA receptor, recent evidence suggests that other receptors such as AMPA, and active metabolites such as nor-ketamine, may also play a role in pain relief and alleviation of depression. Data from clinical studies performed in patients with chronic pain and depression, and the observation that ketamine's analgesic benefits outlast its effects on quantitative sensory testing, suggest that the enduring effects on chronic pain may be predominantly due ketamine's ability to modulate the affective-motivational dimension of pain.
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