Browse by Audience
We aimed to assess if subjects with diabetes exhibit higher prevalence of chronic back pain than age-sex-province of residence-matched non-diabetic controls. We also aimed to identify predictors for chronic neck pain (CNP) or chronic low back pain (CLBP) among subjects with diabetes. A case control study was conducted using data obtained from the Spanish National Health Survey 2017. Multivariable conditional and unconditional logistic regression models were constructed. A total of 2095 diabetes sufferers and 2095 non-diabetic matched controls were analyzed. The prevalence of CNP and CLBP was 27.3% and 34.8%, respectively, in diabetes sufferers and 22.1% and 29.0% in non-diabetes controls (both, < 0.001). After multivariable analysis, the ORs showed significantly higher adjusted risk of CNP (OR 1.34; 95% CI 1.19-1.51) and CLBP (OR 1.19, 95% CI 1.09-1.31) in diabetes cases. Diabetes sufferers with CNP or CLBP showed higher use of pain medication and higher prevalence of migraine/frequent headache than controls. Female sex, worse self-rated health and use of pain medication were predictors for CNP and CLBP in subjects with diabetes. CNP and CLBP are significantly more prevalent in diabetes sufferers than in controls. Current results can help to design better preventive and educational strategies for these highly prevalent and burdensome pains among diabetic patients.
Learn More >Ketamine is a dissociative anesthetic with analgesic properties. Ketamine's analgesic properties have been suggested to result from its dissociative properties. To the authors' knowledge, this postulate is unsubstantiated. The authors hypothesize that the dissociative and analgesic properties of ketamine are independent.
Learn More >Complex regional pain syndrome type 1 (CRPS-1) is a disabling painful disease, with variable outcomes in terms of chronic pain and disability. A long time between onset and diagnosis seems predictive for late recovery and progression toward a chronic disease. This study aims to investigate demographic and clinical variables associated with delayed CRPS-1 diagnosis.
Learn More >Evidence in preclinical models of chronic pain and human psychophysical investigations has suggested that alterations in endogenous brainstem pain-modulation circuit functioning are critical for the initiation and maintenance of pain. Whilst preclinical models have begun to explore the functioning of this circuitry in chronic pain, little is known about such functioning in humans with chronic pain. The aim of this investigation was to determine whether individuals with chronic non-neuropathic pain, painful Temporomandibular Disorders (TMD), display alterations in brainstem pain-modulating circuits. Using resting-state functional magnetic resonance imaging (fMRI), we performed static and dynamic functional connectivity (FC) analyses to assess ongoing circuit function in 16 TMD and 45 control subjects. We calculated static FC as the correlation of fMRI signals between regions over the entire scan and dynamic FC as the correlation of signals in a short (50s) windows. Compared with controls, TMD subjects showed significantly greater (static) FC between the rostral ventromedial medulla and both the subnucleus reticularis dorsalis and the region that receives orofacial nociceptive afferents, the spinal trigeminal nucleus. No differences were found in other brainstem pain-modulating regions such as the midbrain periaqueductal gray matter and locus coeruleus. We also identified that TMD subjects experience greater variability in the dynamic functional connections between the rostral ventromedial medulla and both the subnucleus reticularis dorsalis and spinal trigeminal nucleus. These changes may underlie enhanced descending pain-facilitating actions over the region that receives nociceptive afferents, ultimately leading to enhanced nociceptive transmission to higher brain regions and thus contributing to the ongoing perception of pain. PERSPECTIVE: Psychophysical studies suggest that brainstem pain-modulation circuits contribute to the maintenance of chronic pain. We report that individuals with painful Temporomandibular Disorders (TMD) display altered static and dynamic functional connectivity within the brainstem pain-modulation network. Modifying this circuitry may alter an individual's ongoing pain.
Learn More >Anticonvulsant drugs are used to treat a wide range of non-epileptic conditions, including chronic, neuropathic pain. We obtained a phenoxyalkylaminoalkanol derivative, KM-416 which had previously demonstrated a significant anticonvulsant activity and had also been shown to bind to 5-HT, α-receptors and SERT and not to exhibit mutagenic properties. As KM-416 is a promising compound in our search for drug candidates, in the present study we further assessed its pharmacological profile (analgesic, local anesthetic, and antidepressant-like activities) accompanied with patch-clamp studies. Considering the importance of drug safety, its influence on the cardiovascular system was also evaluated. Moreover, KM-416 was subjected to forced degradation and pharmacokinetic studies to examine its stability and pharmacokinetic parameters. KM-416 revealed a significant antinociceptive activity in the tonic – the formalin test, neurogenic – the capsaicin test, and neuropathic pain model – streptozotocin-induced peripheral neuropathy. Moreover, it exerted a local anesthetic effect. In addition, KM-416 exhibited anti-depressant like activity. The results from the patch-clamp studies indicated that KM-416 can inhibit currents elicited by activation of NMDA receptors, while it also exhibited a voltage-dependent inhibition of Na currents. KM-416 did not influence ventricular depolarization and repolarization. Following oral administration, pharmacokinetics of KM-416 was characterized by a rapid absorption in the rat. The brain-to-plasma AUC ratio was 6.7, indicating that KM-416 was well distributed to brain. The forced degradation studies showed that KM-416 was very stable under stress conditions. All these features made KM-416 a promising drug candidate for further development against neuropathic pain and epilepsy.
Learn More >The opioid crisis has underscored the urgent need to identify safe and effective therapeutic strategies to overcome opioid-induced liabilities. We recently reported that LY2828360, a slowly signaling G protein-biased cannabinoid CB receptor agonist, suppresses neuropathic nociception and attenuates the development of tolerance to the opioid analgesic morphine in paclitaxel-treated mice. Whether beneficial effects of LY2828360 are dependent upon the presence of a pathological pain state are unknown and its impact on unwanted opioid-induced side-effects have never been investigated. Here, we asked whether LY2828360 would produce synergistic anti-allodynic effects with morphine in a paclitaxel model of chemotherapy-induced neuropathic pain and characterized its impact on opioid-induced reward and other unwanted side-effects associated with chronic opioid administration. Isobolographic analysis revealed that combinations of LY2828360 and morphine produced synergistic anti-allodynic effects in suppressing paclitaxel-induced mechanical allodynia. In wildtype (WT) mice, LY2828360 blocked morphine-induced reward in a conditioned place preference assay without producing reward or aversion when administered alone. The LY2828360-induced attenuation of morphine-induced reward was absent in CB knockout (CBKO) mice. In the absence of a neuropathic pain state, LY2828360 partially attenuated naloxone-precipitated opioid withdrawal in morphine-dependent WT mice, and this withdrawal was itself markedly exacerbated in CBKO mice. Moreover, LY2828360 did not reliably alter morphine-induced slowing of colonic transit or attenuate tolerance to morphine antinociceptive efficacy in the hot plate test of acute nociception. Our results suggest that cannabinoid CB receptor activation enhances the therapeutic properties of opioids while attenuating unwanted side-effects such as reward and dependence that occur with sustained opioid treatment.
Learn More >The long-term safety and efficacy of fremanezumab were evaluated in a 52-week extension study (NCT02638103). Patient satisfaction with fremanezumab, dosing preferences, and patient-reported outcomes were assessed in a subpopulation who completed the extension study and consented to a follow-up questionnaire.
Learn More >To investigate the role of IL-33 in gouty arthritis.
Learn More >Today, persistent and uncontrolled inflammation is appreciated to play a pivotal role in many diseases, such as cardiovascular diseases, neurodegenerative diseases, metabolic syndrome and many other diseases of public health concern (e.g. Coronavirus Disease 2019 (COVID-19) and periodontal disease). The ideal response to initial challenge in humans is a self-limited inflammatory response leading to complete resolution. The resolution phase is now widely recognized as a biosynthetically active process, governed by a superfamily of endogenous chemical mediators that stimulate resolution of inflammatory responses, namely specialized proresolving mediators (SPMs). Because resolution is the natural ideal response, the SPMs have gained attention. SPMs are mediators that include ω-6 arachidonic acid-derived lipoxins, ω-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)-derived resolvins, protectins and maresins, cysteinyl-SPMs, as well as n-3 docosapentaenoic acid (DPA)-derived SPMs. These novel immunoresolvents, their biosynthetic pathways and receptors have proven to promote resolution of inflammation, clearance of microbes, reduce pain and promote tissue regeneration via specific cellular and molecular mechanisms. As of 17 August, 2020, PubMed.gov reported >1170 publications for resolvins, confirming their potent protective actions from many laboratories worldwide. Since this field is rapidly expanding, we provide a short update of advances within 2-3 years from human and preclinical animal studies, together with the structural-functional elucidation of SPMs and identification of novel SPM receptors. These new discoveries indicate that SPMs, their pathways and receptors could provide a basis for new approaches for treating inflammation-associated diseases and for stimulating tissue regeneration via resolution pharmacology and precision nutrition.
Learn More >