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Bioorganic & Medicinal Chemistry May 2014The cannabinoid acids are a structurally heterogeneous group of compounds some of which are endogenous molecules and others that are metabolites of phytocannabinoids.... (Review)
Review
The cannabinoid acids are a structurally heterogeneous group of compounds some of which are endogenous molecules and others that are metabolites of phytocannabinoids. The prototypic endogenous substance is N-arachidonoyl glycine (NAgly) that is closely related in structure to the cannabinoid agonist anandamide. The most studied phytocannabinoid is Δ(9)-THC-11-oic acid, the principal metabolite of Δ(9)-THC. Both types of acids have in common several biological actions such as low affinity for CB1 anti-inflammatory activity and analgesic properties. This suggests that there may be similarities in their mechanism of action, a point that is discussed in this review. Also presented are reports on analogs of the acids that provide opportunities for the development of novel therapeutic agents, such as ajulemic acid.
Topics: Analgesics; Animals; Cannabinoids; Dronabinol; Endocannabinoids; Humans; Molecular Structure
PubMed: 24731541
DOI: 10.1016/j.bmc.2014.03.038 -
Cellular and Molecular Life Sciences :... Feb 2018Glycinergic neurotransmission has long been known for its role in spinal motor control. During the last two decades, additional functions have become increasingly... (Review)
Review
Glycinergic neurotransmission has long been known for its role in spinal motor control. During the last two decades, additional functions have become increasingly recognized-among them is a critical contribution to spinal pain processing. Studies in rodent pain models provide proof-of-concept evidence that enhancing inhibitory glycinergic neurotransmission reduces chronic pain symptoms. Apparent strategies for pharmacological intervention include positive allosteric modulators of glycine receptors and modulators or inhibitors of the glial and neuronal glycine transporters GlyT1 and GlyT2. These prospects have led to drug discovery efforts in academia and in industry aiming at compounds that target glycinergic neurotransmission with high specificity. Available data show promising analgesic efficacy. Less is currently known about potential unwanted effects but the presence of glycinergic innervation in CNS areas outside the nociceptive system prompts for a careful evaluation not only of motor function, but also of potential respiratory impairment and addictive properties.
Topics: Analgesics; Animals; Drug Discovery; Drugs, Investigational; Glycine Plasma Membrane Transport Proteins; Humans; Molecular Targeted Therapy; Receptors, Glycine
PubMed: 28791431
DOI: 10.1007/s00018-017-2622-x -
Journal of Enzyme Inhibition and... Dec 2018Twelve new derivatives of benzothiazole bearing benzenesulphonamide and carboxamide were synthesised and investigated for their in vivo anti-inflammatory, analgesic and...
Twelve new derivatives of benzothiazole bearing benzenesulphonamide and carboxamide were synthesised and investigated for their in vivo anti-inflammatory, analgesic and ulcerogenic activities. Molecular docking showed an excellent binding interaction of the synthesised compounds with the receptors, with 17c showing the highest binding energy (-12.50 kcal/mol). Compounds 17c and 17i inhibited carrageenan-induced rat paw oedema at 72, 76, and 80% and 64, 73, and 78% at 1 h, 2 h, and 3 h, respectively. In the analgesic activity experiment, compounds 17c, 17 g, and 17i had ED (µM/kg) of 96, 127, and 84 after 0.5 h; 102, 134, and 72 after 1 h and 89, 156, and 69 µM/kg after 2 h, respectively, which were comparable with 156, 72, and 70 µM/kg for celecoxib. The ulcerogenic index of the most active derivatives 17c and 17i were 0.82 and 0.89, respectively, comparable to 0.92 for celecoxib. The physicochemical studies of the new derivatives showed that they will not have oral bioavailability problems.
Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Benzothiazoles; Edema; Male; Mice; Molecular Docking Simulation; Molecular Structure; Rats; Ulcer
PubMed: 29372659
DOI: 10.1080/14756366.2018.1426573 -
BMJ (Clinical Research Ed.) Feb 1995
Topics: Analgesics; Headache; Humans
PubMed: 7888879
DOI: 10.1136/bmj.310.6978.479 -
The Journal of Pain Feb 2023The 0 to 10 numeric rating scale of pain intensity is a standard outcome in randomized controlled trials (RCTs) of pain treatments. For individuals taking analgesics,...
The 0 to 10 numeric rating scale of pain intensity is a standard outcome in randomized controlled trials (RCTs) of pain treatments. For individuals taking analgesics, there may be a disparity between "observed" pain intensity (pain intensity with concurrent analgesic use) and pain intensity without concurrent analgesic use (what the numeric rating scale would be had analgesics not been taken). Using a contemporary causal inference framework, we compare analytic methods that can potentially account for concurrent analgesic use, first in statistical simulations, and second in analyses of real (non-simulated) data from an RCT of lumbar epidural steroid injections. The default analytic method was ignoring analgesic use, which is the most common approach in pain RCTs. Compared to ignoring analgesic use and other analytic methods, simulations showed that a quantitative pain and analgesia composite outcome based on adding 1.5 points to pain intensity for those who were taking an analgesic (the QPAC) optimized power and minimized bias. Analyses of real RCT data supported the results of the simulations, showing greater power with analysis of the QPAC as compared to ignoring analgesic use and most other methods examined. We propose alternative methods that should be considered in the analysis of pain RCTs. PERSPECTIVE: This article presents the conceptual framework behind a new quantitative pain and analgesia composite outcome, the QPAC, and the results of statistical simulations and analyses of trial data supporting improvements in power and bias using the QPAC. Methods of this type should be considered in the analysis of pain RCTs.
Topics: Humans; Analgesics, Opioid; Randomized Controlled Trials as Topic; Analgesics; Pain Management; Pain; Pain, Postoperative
PubMed: 36220482
DOI: 10.1016/j.jpain.2022.09.017 -
Alcoholism, Clinical and Experimental... Aug 2022Although recent literature provides promising support for the analgesic properties of alcohol, potential differences in alcohol analgesia as a function of chronic pain... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Although recent literature provides promising support for the analgesic properties of alcohol, potential differences in alcohol analgesia as a function of chronic pain status are not well understood. Thus, this study examined chronic pain status as a potential moderator of alcohol analgesia and distinguished between multiple aspects of pain experience and sensitivity: pain threshold, pain intensity, pain unpleasantness, and perceived relief.
METHODS
Social drinkers with (N = 19) and without (N = 29) chronic jaw pain completed two testing sessions in a counterbalanced order: alcohol (target BrAC = 0.08 g/dl) and placebo. In each, pressure algometry was performed at the insertion of the masseter. Alcohol analgesia was assessed by examining the main and interactive effects of beverage condition, pressure level (4, 5, or 6 pound-feet [lbf]), and chronic jaw pain status (chronic pain vs. pain-free control) on quantitative sensory testing measures and pain relief ratings following noxious stimuli.
RESULTS
Analyses indicated significant increases in pain threshold and pain relief and reductions in pain unpleasantness and pain intensity, under the alcohol condition. Chronic pain participants demonstrated lower pain thresholds and greater pain intensity and pain unpleasantness ratings than controls. There were no interactive effects of alcohol and pain conditions on any pain measure.
CONCLUSIONS
Findings provide experimental evidence of alcohol's analgesic and pain-relieving effects and suggest that these effects do not significantly differ by chronic pain status. Individuals, who self-medicate pain via alcohol consumption, irrespective of pain status, may be at increased risk to engage in hazardous drinking patterns and thus experience adverse alcohol-related consequences.
Topics: Adult; Alcohol Drinking; Analgesics; Chronic Pain; Ethanol; Humans; Pain Measurement; Pain Threshold
PubMed: 35989585
DOI: 10.1111/acer.14883 -
AMA Journal of Ethics Aug 2020The opioid epidemic challenges current attitudes toward pain management and necessitates the reexamination of the World Health Organization (WHO) 3-step analgesic... (Review)
Review
The opioid epidemic challenges current attitudes toward pain management and necessitates the reexamination of the World Health Organization (WHO) 3-step analgesic ladder, introduced in 1986 for cancer pain management. Surgical treatment of pain is a logical extension of the original guideline, which is often absent in conversations with patients about treatment options for their pain and consequentially underutilized. However, with concerns growing regarding opioid use, a shift in the stepwise approach of the WHO analgesic ladder in an age of developing technology and surgical offerings could have profound implications for patients and public health. Surgical interventions potentially provide a long-term, cost-effective management strategy to reduce opioid use. This review canvasses surgical options, highlights literature on failed back surgery syndrome and spinal cord stimulation and reconsiders the current ladder approach to pain management.
Topics: Analgesics; Analgesics, Opioid; Humans; Neoplasms; Pain; Pain Management; World Health Organization
PubMed: 32880358
DOI: 10.1001/amajethics.2020.695 -
Pharmacological Reports : PR Oct 2022To verify the validity of the proposed pain treatment approach, which is based on concomitant blocking of the Transient Receptor Potential Ankyrin 1 (TRPA1) channel and...
BACKGROUND
To verify the validity of the proposed pain treatment approach, which is based on concomitant blocking of the Transient Receptor Potential Ankyrin 1 (TRPA1) channel and phosphodiesterases (PDEs) 4B/7A activity, we continued our pharmacological studies on 8-alkoxypurine-2,6-diones selected based on previous in vitro screening.
METHODS
Derivatives 17, 31, and 36 were pharmacologically evaluated in vivo using the formalin test and oxaliplatin-induced neuropathic pain: the von Frey and the cold plate tests, and in the carrageenan-induced edema model. Compound 36, which turned out to be the most promising, was further evaluated in the collagen-induced arthritis model. The pharmacokinetic parameters of this compound were also estimated.
RESULTS
All the tested compounds exhibited significant analgesic and anti-inflammatory activities. Compound 36 was additionally characterized by an antiarthritic effect and showed a favorable pharmacokinetic profile in rats.
CONCLUSION
The compounds evaluated in this study represent a new class of derivatives with analgesic and anti-inflammatory activities that involve TRPA1 antagonism and PDE4/7 inhibition.
Topics: Animals; Rats; TRPA1 Cation Channel; Carrageenan; Oxaliplatin; Ankyrins; Analgesics; Anti-Inflammatory Agents; Transient Receptor Potential Channels; Purines; Phosphoric Diester Hydrolases
PubMed: 35930193
DOI: 10.1007/s43440-022-00397-6 -
Pain Medicine (Malden, Mass.) Jan 2019Analyzing medication data for research purposes is complex, and methods are rarely described in the literature. Our objective was to describe methods of quantifying...
OBJECTIVES
Analyzing medication data for research purposes is complex, and methods are rarely described in the literature. Our objective was to describe methods of quantifying opioid and nonopioid analgesics and to compare the utility of five different analgesic coding methods when analyzing relationships between pain, analgesic use, and clinical outcomes. In this study, we used physical function as the outcome variable for its clinical relevance and its relationship to pain in older adults.
DESIGN
Secondary analyses of baseline cross-sectional data from the Advanced Cognitive Training Interventions for Vital Elders (ACTIVE) study.
SETTING
Community settings in six regions of the United States.
SUBJECTS
A total of 2,802 community-residing adults older than age 65 years.
METHODS
A medication audit was conducted. Analgesics were coded as any pain medication, counts (total analgesics, number of opioids and nonopioids), equianalgesics (oral morphine equivalents, oral acetaminophen equivalents), and dose categories. Adjuvant medications used to treat pain (e.g., tricyclic antidepressants and anticonvulsants) and low-dose aspirin typically used for cardiovascular conditions were excluded from these analyses. To examine the utility of these various approaches, a series of hierarchical regression models were conducted with pain and analgesics as predictors and physical functioning as the dependent variable.
RESULTS
Eighty-one point nine percent of participants reported experiencing recent pain, but 26% reported analgesic use. Nonopioids were the most common drug class used. Models revealed that pain was significantly associated with worse physical function (β = -0.45, P = 0.001), after controlling for demographic and analgesic variables. Two basic drug coding methods (e.g., any pain medication, number of pain medications) were equivalent in their explanatory power (β = -0.12, P = 0.001) and were slightly stronger predictors of function than the more complex coding procedures.
CONCLUSIONS
Analgesic medications are important variables to consider in community-based studies of older adults. We illustrate several methods of quantifying analgesic medications for research purposes. In this community-based sample, we found no advantage of complex equianalgesic coding methods over simple counts in predicting physical functioning. The results may differ depending on the research question or clinical outcome studied. Thus, methods of analyzing analgesic drug data warrant further research.
Topics: Acetaminophen; Aged; Aged, 80 and over; Aging; Analgesics; Analgesics, Non-Narcotic; Analgesics, Opioid; Cross-Sectional Studies; Female; Humans; Independent Living; Male; Morphine; Pain
PubMed: 29408973
DOI: 10.1093/pm/pnx340 -
The American Journal of Medicine Jul 1998Pain affects everyone at some point in their life. However, everyone experiences pain in a highly individualized way, and therefore, the management of pain must also be... (Review)
Review
Pain affects everyone at some point in their life. However, everyone experiences pain in a highly individualized way, and therefore, the management of pain must also be customized. Of the 3 general types of pain-acute, chronic malignant, and chronic nonmalignant-the latter is the least predictable and, therefore, can be the most difficult to treat. General principles of pain management can be summarized as (1) respecting the pain and the patient; (2) recognizing and addressing the psychosocial aspects of pain; and (3) treating the pain-and the underlying cause-appropriately and in a timely fashion. The best success in pain management relies on a multidisciplinary approach that includes patient education, medications, physical medicine, and psychological counseling. Although a number of effective analgesic drugs are available, all are associated with adverse events. To reduce the risk of these side effects, the patient's specific needs and medical history must be considered before initiating therapy. Central to effective management of chronic pain is a positive physician-patient relationship. Several strategies are discussed to help in building such a connection.
Topics: Analgesics; Humans; Pain; Pain Management; Physician-Patient Relations; Social Support
PubMed: 9715828
DOI: 10.1016/s0002-9343(98)00068-0