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Most canine visits to veterinarians are related to skin diseases with itch being the chief complaint. Historically, several itch-inducing molecules and pathways have been identified in mice, but whether or not these are similar in dogs is not yet known. Herein, we set out to study the expression of pruritogenic neuropeptides, their cognate receptors with a limited functional validation thereof using a multidisciplinary approach. We demonstrated the expression of somatostatin and other major neuropeptides and receptors in canine dorsal root ganglia neurons. Next, we showed that interleukin-31, serotonin, and histamine activate such neurons. Furthermore, we demonstrated the physiological release of somatostatin from dog dorsal root ganglia neurons in response to several endogenous itch mediators. In summary, our results provide the first evidence that dogs use similar pruritogenic pathways to those characterized in mice and we thus identify multiple targets for the future treatment of itch in dogs.
In randomised, controlled trials (RCTs) of oral drug treatment of migraine attacks, efficacy is evaluated after 2 hours. The effect of oral naratriptan 2.5 mg with a maximum blood concentration (T ) at 2 hours increases from 2 to 4 hours in RCTs. To check whether such a delayed effect is also present for other oral antimigraine drugs, we hand-searched the literature for publications on RCTs reporting efficacy. Two triptans, three non-steroidal anti-inflammatory drugs (NSAIDs), a triptan combined with an NSAID, and a calcitonin gene-related peptide receptor antagonist were evaluated for their therapeutic gain with determination of time to maximum effect (E ). E was compared with known T from pharmacokinetic studies to estimate the delay to pain-free. The delay in therapeutic gain varied from 1-2 hours for zolmitriptan 5 mg to 7 hours for naproxen 500 mg. An increase in effect from 2 to 4 hours was observed after eletriptan 40 mg, frovatriptan 2.5 mg, and lasmiditan 200 mg, and after rizatriptan 10 mg (T = 1 h) from 1 to 2 hours. This strongly indicates a general delay of effect in oral antimigraine drugs. A review of five possible effects of triptans on the trigemino-vascular system did not yield a simple explanation for the delay. In addition, E for triptans probably depends partly on the rise in plasma levels and not only on its maximum. The most likely explanation for the delay in effect is that a complex "antimigraine system" with more than one site of action is involved.
This trial evaluated the efficacy and safety of GZ389988A, a tropomyosin receptor kinase A (TrkA) inhibitor, in subjects with painful knee osteoarthritis (OA).
To identify the differences in overall occurrence, location, and disease burden of white matter hyperintensities (WMH) in patients with sporadic hemiplegic migraine (SHM) and patients with migraine headaches.
With governments' increasing efforts to curb opioid prescription use and limit dose below the Centers for Disease Control and Prevention (CDC)-recommended threshold of 90 morphine milligram equivalents per day, little is known about prescription opioid patterns preceding opioid use disorder (OUD) or overdose. This study aimed to determine prescribed opioid fills and dose trajectories in the year before an incident OUD or overdose diagnosis using a 2005-2016 commercial healthcare database.
To describe neuronal networks underlying commonly reported migraine premonitory symptoms and to discuss how these might precipitate migraine pain.
Exercise is considered an important component of effective chronic pain management and it is well established that long term exercise training provides pain relief. In healthy, pain-free populations, a single bout of aerobic or resistance exercise typically leads to exercise induced hypoalgesia (EIH), a generalized reduction in pain and pain sensitivity that occurs during exercise and for some time afterwards. In contrast, EIH is more variable in chronic pain populations and is more frequently impaired; with pain and pain sensitivity decreasing, remaining unchanged or, in some cases, even increasing in response to exercise. Pain exacerbation with exercise may be a major barrier to adherence, precipitating a cycle of physical inactivity that can lead to long-term worsening of both pain and disability. In order to optimize the therapeutic benefits of exercise, it is important to understand how EIH works, why it may be impaired in some people with chronic pain and how this should be addressed in clinical practice. In this article, we provide an overview of EIH across different chronic pain conditions. We discuss possible biological mechanisms of EIH and the potential influence of sex and psychosocial factors, both in pain-free adults and, where possible, individuals with chronic pain. Clinical implications of impaired EIH are discussed and recommendations are made for future research, including further exploration of individual differences in EIH, the relationship between exercise dose and EIH, the efficacy of combined treatments and the use of alternative measures to quantify EIH. Perspective: This article provides a contemporary review of the acute effects of exercise on pain and pain sensitivity, including in people with chronic pain conditions. Existing findings are critically reviewed, clinical implications are discussed and recommendations are offered for future research.
Involvement of Endothelin Receptors in Peripheral Sensory Neuropathy Induced by Oxaliplatin in Mice.
The aim of this study was to evaluate the participation of the endothelin ET and ET receptors and the effects of bosentan in oxaliplatin-induced peripheral sensory neuropathy (OIN) in mice. Adult male Swiss mice received 1 mg/kg of oxaliplatin intravenously, twice a week for 5 weeks. Dorsal root ganglia (DRG) and spinal cords were removed for evaluation of the endothelin ET and ET receptor expression. Afterwards, selective (BQ-123 and BQ-788; 10 nmol in 30 μL, intraplantarly) and non-selective (bosentan, 100 mg/kg, orally) antagonists were administered in order to evaluate the involvement of the endothelin receptors in OIN. Mechanical and thermal nociception tests were performed once a week for 56 days. Oxaliplatin induced mechanical and thermal hypersensitivity and increased the endothelin ET receptor expression in both the DRG and spinal cord (P < 0.05). Endothelin ET receptor expression was increased in the DRG (P < 0.05) but not in the spinal cord. Both endothelin ET and ET receptor selective antagonists partially prevented mechanical hyperalgesia in mice with OIN (P < 0.05). Moreover, bosentan prevented mechanical and thermal hypersensitivity in oxaliplatin-treated mice (P < 0.05). In conclusion, both endothelin ET and ET receptors seem to be involved in the OIN in mice and they should be considered possible targets for the management of this clinical feature.
Musculoskeletal pain reduces corticomotor excitability (CE) and methods modulating such CE reduction remain elusive. This study aimed to modulate pain-induced CE reduction by performing action observation and motor imagery (AOMI) during experimental muscle pain. Twelve healthy subjects participated in three cross-over and randomized sessions separated by one week. During the AOMI session subjects performed an AOMI task for 10 mins. In the AOMI+PAIN session, hypertonic saline was injected in the first dorsal interosseous (FDI) muscle prior to performing the AOMI task. In the PAIN session, subjects remained at rest for 10 min or until pain-resolve after the hypertonic saline injection. CE was assessed using transcranial magnetic stimulation motor-evoked potentials (TMS-MEPs) of the FDI muscle at baseline, during, immediately after, and 10 min after AOMI and/or PAIN. Facilitated TMS-MEPs were found after two and four mins of AOMI performance (P<0.017) whereas a reduction in TMS-MEPs appeared at four mins (P<0.017) during the PAIN session. Performing the AOMI task during pain counteracted the reduction in CE, as evident by no change in TMS-MEPs during the AOMI+PAIN session (P>0.017). Pain intensity was similar between the AOMI+PAIN and PAIN sessions (P=0.71). This study, that may be considered a pilot, demonstrated the counteracting effects of AOMI on pain-induced reduction in CE and warrants further studies in a larger population. PERSPECTIVE: This is the first study to demonstrate a method counteracting the reduction in corticomotor excitability associated with acute pain and advances therapeutic possibilities for individuals with chronic musculoskeletal pain.
Botulinum toxin A (BTX-A) is a promising therapeutic modality against trigeminal neuralgia (TN) with certain controversies pertaining to its application. To provide further information on factors influencing the treatment outcomes of BTX-A, a retrospective study with 152 patients with TN treated with BTX-A was performed. The starting time and duration of the therapeutic effect, as well as side effects, of BTX-A in the treatment of TN were analyzed by sex, age, course of disease, number of branches and injected dose. A total of 136 patients exhibited symptom improvement within 2 weeks following BTX-A treatment as evaluated using a visual analog scale (VAS). The effect of BTX-A was sustained throughout the initial 6 months of the follow-up and was demonstrated to persist for as long as 28 months. Female sex, short disease course and high injection dose (>70 units) were associated with lower long-term VAS scores. Patients receiving short-term medium-(50-70 units) or high-dose injections were more likely to be completely cured. Patients with a median disease course (1-10 years) or multiple branches were more likely to exhibit facial asymmetry. Based on the stratified analysis, female patients with a median disease course (1-10 years) exhibited a higher incidence of side effects and male patients achieved better treatment outcomes with high BTX-A doses. BTX-A effectively alleviated patients with TN in both short or long term, although the treatment efficacy may depend on patient characteristics.