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Adverse life experiences (ALEs) are associated with hyperalgesia and chronic pain, but the underlying mechanisms are poorly understood. One potential mechanism is hyperexcitability of spinal neurons (ie, central sensitization). Given that Native Americans (NAs) are more likely to have ALEs and to have a higher prevalence of chronic pain, the relationship between ALEs and spinal hyperexcitability might contribute to their pain risk. The present study assessed temporal summation of the nociceptive flexion reflex (TS-NFR; a correlate of spinal hyperexcitability) and pain (TS-Pain) in 246 healthy, pain-free non-Hispanic whites and NAs. The Life Events Checklist was used to assess the number of ALEs. Multilevel growth models were used to predict TS-NFR and TS-Pain, after controlling for age, perceived stress, psychological problems, negative and positive affect, and painful stimulus intensity. ALEs and negative affect were significantly associated with greater pain, but not enhanced TS-Pain. By contrast, ALEs were associated with enhanced TS-NFR. Race did not moderate these relationships. This finding implies that ALEs promote hyperalgesia as a result of increased spinal neuron excitability. Although relationships between ALEs and the nociceptive flexion reflex/pain were not stronger in NAs, given prior evidence that NAs experience more ALEs, this factor might contribute to the higher prevalence of chronic pain in NAs. PERSPECTIVE: This study found a dose-dependent relationship between ALEs and spinal neuron excitability. Although the relationship was not stronger in NAs than non-Hispanic whites, given prior evidence that NAs experience more ALEs, this could contribute to the higher prevalence of chronic pain in NAs.
Learn More >Chronic musculoskeletal pain (CMSP) disorders are among the most prevalent and disabling conditions worldwide. It would be advantageous to have common outcome measures when comparing results across different CMSP research studies.
Learn More >High voltage-activated (HVA) Ca (Ca) channels are oligomeric complexes formed by an ion-conducting main subunit (Cavα) and at least two auxiliary subunits (Cavβ and Caαδ). It has been reported that the expression of Caαδ1 increases in the dorsal root ganglia (DRGs) of animals with mechanical allodynia, and that the transcription factor Sp1 regulates the expression of the auxiliary subunit. Hence, the main aim of this work was to investigate the role of Sp1 as a molecular determinant of the exacerbated expression of Caαδ-1 in the nerve ligation-induced model of mechanical allodynia. Our results show that ligation of L5/L6 spinal nerves (SNL) produced allodynia and increased the expression of Sp1 and Caαδ-1 in the DRGs. Interestingly, intrathecal administration of the Sp1 inhibitor mithramycin A (Mth) prevented allodynia and decreased the expression of Sp1 and Caαδ-1. Likewise, electrophysiological recordings showed that incubation with Mth decreased Ca current density in the DRG neurons, acting mostly on HVA channels. These results suggest that L5/L6 SNL produces mechanical allodynia and increases the expression of the transcription factor Sp1 and the subunit Caαδ-1 in the DRGs, while Mth decreases mechanical allodynia and Ca currents through HVA channels in sensory neurons by reducing the functional expression of the Caαδ-1 subunit.
Learn More >Chronic pain states have resulted in an overreliance on opioid pain relievers, which can carry significant risks when used long term. As such, alternative pain treatments are increasingly desired. Although emerging research suggests that cannabinoids have therapeutic potential regarding pain, results from studies across pain populations have been inconsistent. To provide meta-analytic clarification regarding cannabis's impact on subjective pain, we identified studies that assessed drug-induced pain modulations under cannabinoid and corresponding placebo conditions. A literature search yielded 25 peer-reviewed records that underwent data extraction. Baseline and end-point data were used to compute standardized effect size estimates (Cohen's d) across cannabinoid administrations (k = 39) and placebo administrations (k = 26). Standardized effects were inverse-variance weighted and pooled across studies for meta-analytic comparison. Results revealed that cannabinoid administration produced a medium-to-large effect across included studies, Cohen's d = -0.58, 95% confidence interval (CI) [-0.74, -0.43], while placebo administration produced a small-to-medium effect, Cohen's d = -0.39, 95% CI [-0.52, -0.26]. Meta-regression revealed that cannabinoids, β = -0.43, 95% CI [-0.62, -0.24], p < .05, synthetic cannabinoids, β = -0.39, 95% CI [-0.65, -0.14], p < .05, and sample size, β = 0.01, 95% CI [0.00, 0.01], p < .05, were associated with marked pain reduction. These outcomes suggest that cannabinoid-based pharmacotherapies may serve as effective replacement/adjunctive options regarding pain, however, additional research is warranted. Additionally, given demonstrated neurocognitive side effects associated with some constituent cannabinoids (i.e., THC), subsequent work may consider developing novel therapeutic agents that capitalize on cannabis's analgesic properties without producing adverse effects. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Learn More >The present study aimed at investigating both the early and long-term effects of maternal deprivation as well as gender on neuromotor reflexes, anxiety behavior and thermal nociceptive responses. A total of 64 Wistar rats pups (32 males, 32 females) were utilized and were deprived of their mother for 3 h/daily, from postnatal day 1 (P1) until P10. Successively, animals were divided into 2 groups: control group (C) – pups no subjected to intervention; and the maternal-deprived group (MD): pups subjected to maternal deprivation. The neuromotor reflexes were evaluated through the righting reflex and negative geotaxis tests; the exploratory behavior by open field test (OFT); the anxiety-like behavior by elevated plus-maze test (EPM); the thermal nociceptive responses byhot plate (HP) and tail-flick (TFL) tests. All the animals subjected to maternal deprivation showed a delayed reflex response at P8 in the negative geotaxis test. In contrast, the OFT at P20 identified an effect of gender on the outer crossings and grooming as well as an interaction between gender and maternal deprivation on latency. Additionally, effect of maternal deprivation in the open and closed arms as well as gender effect in the protected head-dipping (PHD) and non-protected head-dipping (NPHD) were observed at P20 (EPM). In contrast, there were a gender effect on latency and an interaction between gender and maternal deprivation on rearing at P42. Moreover, in nociceptive tests was observed an analgesic effect induced by maternal deprivation; however, in the TFL test, only deprived females showed this effect. Surprisingly, only control animals presented an ontogeny nociceptive effect in the HP testat P21 and P43, which may be related to an increase in the inhibitory nociceptive pathways throughout life. In this way, we suggest maternal deprivation to be able to anticipate the maturation of the inhibitory nociceptive pathway. In conclusion, maternal deprivation induced a delayed reflex response at P8 and altered the anxiety and nociceptive behaviors according to the time after exposure to this stressor, in a gender-specific manner.
Learn More >Chronic pain is common after spinal cord injury (SCI) and dedicated SCI cognitive behavioural therapy pain management programmes (CBT-PMPs) have a growing evidence-base to support their uptake clinically. The development of internet-delivered treatment options may overcome barriers to the access and uptake of centre-based programmes. This study examines such an approach on quality of lie (QoL), pain, mood and sleep.
Learn More >Although evolutionarily conserved to expel ectoparasites and aid in the clearance of toxins and noxious environmental stimuli from the host, the type 2 immune response can become pathologic in the setting of a variety of allergic disorders. Itch can be a behavioral extension of type 2 immunity by evoking scratching and, in the setting of disease, can become chronic and thus highly pathologic as well. Classically, our understanding of itch mechanisms has centered around the canonical IgE-mast cell-histamine axis. However, therapies aimed at blocking the histaminergic itch pathway have been largely ineffective, suggesting the existence of nonhistaminergic itch pathways. Indeed, recent advances in itch biology have provided critical new insight into a variety of novel therapeutic avenues for chronic itch in the setting of a number of allergic disorders. Here we highlight how these new developments will likely inform the problem of pruritus in a variety of well-established and emerging conditions in the field of allergy.
Learn More >Painful chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and treatment-resistant sequela of many chemotherapeutic medications. Ligands of α2δ subunits of voltage-gated Ca channels, such as pregabalin, have shown efficacy in reducing mechanical sensitivity in animal models of neuropathic pain. In addition, some data suggest that pregabalin may be more efficacious in relieving neuropathic pain in subjects with increased sensitivity to pinprick. We hypothesized that greater mechanical sensitivity, as quantified by decreased mechanical pain threshold at the feet, would be predictive of a greater reduction in average daily pain in response to pregabalin vs placebo. In a prospective, randomized, double-blinded study, 26 patients with painful CIPN from oxaliplatin, docetaxel, or paclitaxel received 28-day treatment with pregabalin (titrated to maximum dose 600 mg per day) and placebo in crossover design. Twenty-three participants were eligible for efficacy analysis. Mechanical pain threshold was not significantly correlated with reduction in average pain (P = 0.97) or worst pain (P = 0.60) in response to pregabalin. There was no significant difference between pregabalin and placebo in reducing average daily pain (22.5% vs 10.7%, P = 0.23) or worst pain (29.2% vs 16.0%, P = 0.13) from baseline. Post hoc analysis of patients with CIPN caused by oxaliplatin (n = 18) demonstrated a larger reduction in worst pain with pregabalin than with placebo (35.4% vs 14.6%, P = 0.04). In summary, baseline mechanical pain threshold tested on dorsal feet did not meaningfully predict the analgesic response to pregabalin in painful CIPN.
Learn More >To identify the possible prevalence of 'central sensitisation', in patients with chronic recalcitrant lower limb tendinopathy conditions, with the Central Sensitisation Inventory (CSI) questionnaire.
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