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Tapentadol, an analgesic with a dual mechanism of action, involving both μ-opioid receptor agonism and noradrenaline reuptake inhibition (MOP-NRI), was designed for the treatment of moderate to severe pain. However, the widely acknowledged risk of analgesic tolerance and development of physical dependence following sustained opioid use may hinder their effectiveness. One of the possible mechanisms behind these phenomena are alterations in nitric oxide synthase (NOS) system activity. The aim of the study was to investigate the tolerance and dependence potential of tapentadol in rodent models and to evaluate the possible role of nitric oxide (NO) in these processes. Our study showed that chronic tapentadol treatment resulted in tolerance to its antinociceptive effects to an extent similar to tramadol, but much less than morphine. A single injection of a non-selective NOS inhibitor, N-nitro-L-arginine (L-NOArg), reversed the tapentadol tolerance. In dependence studies, repeated administration of L-NOArg attenuated naloxone-precipitated withdrawal in tapentadol-treated mice, whereas a single injection of L-NOArg was ineffective. Biochemical analysis revealed that tapentadol decreased nNOS protein levels in the dorsal root ganglia of rats following 31 days of treatment, while no significant changes were found in iNOS and eNOS protein expression. Moreover, pre-treatment with L-NOArg augmented tapentadol antinociception in an opioid- and α-adrenoceptor-dependent manner. In conclusion, our data suggest that the NOS system plays an important role in the attenuation of tapentadol-induced tolerance and withdrawal. Thus, inhibition of NOS activity can serve as a promising treatment option for long-term tapentadol use by extending its effectiveness and improving the side-effects profile.
Learn More >Opioids are the most commonly prescribed analgesics in the United States. Current guidelines have proposed education initiatives to reduce the risk of chronic opioid consumption, yet there is lack of efficacy data on such interventions. Our study evaluates the impact of perioperative opioid education on postoperative opioid consumption patterns including opioid cessation, number of pills consumed, and opioid prescription refills.
Learn More >Recent studies indicate that the assessment of conditioned pain modulation (CPM) responses and emotional factors can provide important information regarding chronification mechanisms, choices for more efficient therapeutic strategies, and clinical variables supporting a therapeutic prognosis.
Learn More >We compared the incremental effects of adding acceptance and commitment therapy (ACT) to pharmacological treatment as usual (TAU) in a sample of patients with high frequency episodic migraine without aura (HFEM), assessing impact on a spectrum of measures across multiple domains.
Learn More >To evaluate the impact of fremanezumab on the severity and duration of remaining migraine attacks in patients with chronic migraine (CM) or episodic migraine (EM).
Learn More >Gabapentin is commonly prescribed for chronic pain, including to patients with HIV (PWH). There is growing concern regarding gabapentin's potential for harm, particularly in combination with opioids. Among PWH, we examined factors associated with higher doses of gabapentin receipt and determined if receipt varied by opioid use. We examined data from the Veterans Aging Cohort Study, a national prospective cohort including PWH, from 2002 through 2017. Covariates included prescribed opioid dose, self-reported past year opioid use, and other sociodemographic and clinical variables. We used multinomial logistic regression to determine independent predictors of gabapentin receipt. Among 3,702 PWH, 902 (24%) received any gabapentin during the study period at a mean daily dose of 1,469 mg. In the multinomial model, high-dose gabapentin receipt was associated with high-dose benzodiazepine receipt (adjusted odds ratio [aOR], 95% confidence interval [CI]= 1.53, [1.03-2.27]), pain interference (1.65 [1.39-1.95]), and hand or foot pain (1.81, [1.45-2.26]). High-dose gabapentin receipt was associated with prescribed high-dose opioids receipt (2.66 [1.95-3.62]) but not self-reported opioid use (1.03 [0.89-1.21]). PWH prescribed gabapentin at higher doses are more likely to receive high-dose opioids and high-dose benzodiazepines, raising safety concerns.
Learn More >Neuroinflammation has an important role in the pathophysiology of migraine, which is a complex neuro-glio-vascular disorder. The main aim of this review is to highlight findings of cortical spreading depolarization (CSD)-induced neuroinflammatory signaling in brain parenchyma from the inflammasome perspective. In addition, we discuss the limited data of the contribution of inflammasomes to other aspects of migraine pathophysiology, foremost the activation of the trigeminovascular system and thereby the generation of migraine pain.
Learn More >To review the pharmacology, efficacy, and safety of ubrogepant as an abortive migraine treatment.
Learn More >Sleep health is an important factor across several physical and mental health disorders, and a growing scientific consensus has identified sleep as a critical component of opioid use disorder (OUD), both in the active disease state and during OUD recovery. The goal of this narrative review is to collate the literature on sleep, opioid use, and OUD as a means of identifying therapeutic targets to improve OUD treatment outcomes. Sleep disturbance is common and often severe in persons with OUD, especially during opioid withdrawal, but also in persons on opioid maintenance therapies. There is ample evidence that sleep disturbances including reduced total sleep time, disrupted sleep continuity, and poor sleep quality often accompany negative OUD treatment outcomes. Sleep disturbances are bidirectionally associated with several other factors related to negative treatment outcomes, including chronic stress, stress reactivity, low positive affect, high negative affect, chronic pain, and drug craving. This constellation of outcome variables represents a more comprehensive appraisal of the quality of life and quality of recovery than is typically assessed in OUD clinical trials. To date, there are very few clinical trials or experimental studies aimed at improving sleep health in OUD patients, either as a means of improving stress, affect, and craving outcomes, or as a potential mechanistic target to reduce opioid withdrawal and drug use behaviors. As such, the direct impact of sleep improvement in OUD patients is largely unknown, yet mechanistic and clinical research suggests that therapeutic interventions that target sleep are a promising avenue to improve OUD treatment. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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