Browse by Audience
Pain is the most common reason for patients to consult primary care providers. Identification of effective treatments with minimal adverse events is critical to safer opioid-sparing and multi-modal approaches to pain treatment. Topical analgesic patches target medication to peripheral sites of pain while potentially avoiding adverse effects associated with systemic medications. Opioids, prescription nonsteroidal anti-inflammatory drugs, and over-the-counter oral medications are associated with systemic toxicities, increasing morbidity and mortality. This study evaluated a topical analgesic pain-relieving patch in reducing pain severity and improving function in patients with mild to moderate arthritic, neurological, or musculoskeletal pain.
Learn More >Better understanding of the episodic cancer pain (CP) spectrum, including pains that occur in addition to its conventionally defined breakthrough CP (BTcP) and incident CP (IcP) components, may inform CP assessment and management. This study aimed to determine the prevalence of episodic patient-reported CP and the prevalence and associations of study-defined BTcP (S-BTcP) and IcP (S-IcP) in patients with CP.
Learn More >Diabetic peripheral neuropathic pain (DPNP) is the most devastating complication of diabetes mellitus. Unfortunately, successful therapy for DPNP remains a challenge because its pathogenesis is still elusive. However, DPNP is believed to be due partly to abnormal hyperexcitability of dorsal root ganglion (DRG) neurons, but the relative contributions of specific functional subtypes remain largely unknown. Here, using the strepotozotocin (STZ) rat model of DPNP induced by a STZ injection (60 mg/kg, i.p), and intracellular recordings of action potentials (APs) from DRG neurons in anesthetized rats, we examined electrophysiological changes in C-and Aβ-nociceptive and Aβ-low threshold mechanoreceptive (LTM) neurons that may contribute to DPNP. Compared with control, we found in STZ-rats with established pain hypersensitivity (5 weeks post-STZ) several significant changes including: (a) A 23% increase in the incidence of spontaneous activity (SA) in Aβ-LTMs (but not C-mechanosensitive nociceptors) that may cause dysesthesias/paresthesia suffered by DPNP patients, (b) membrane hyperpolarization and a ∼85% reduction in SA rate in Aβ-LTMs by K7 channel activation with retigabine (6 mg/kg, i.v.) suggesting that K7/M channels may be involved in mechanisms of SA generation in Aβ-LTMs, (c) decreases in AP duration and in duration and amplitude of afterhyperpolarization (AHP) in C-and/or Aβ-nociceptors. These faster AP and AHP kinetics may lead to repetitive firing and an increase in afferent input to the CNS and thereby contribute to DPNP development, and (d) a decrease in the electrical thresholds of Aβ-nociceptors that may contribute to their sensitization, and thus to the resulting hypersensitivity associated with DPNP.
Learn More >Disruption of blood-brain barrier integrity and dramatic failure of brain ion homeostasis including fluctuations of pH occurs during cortical spreading depression (CSD) events associated with several neurological disorders, including migraine with aura, traumatic brain injury and stroke. NHE1 is the primary regulator of pH in the central nervous system. The goal of the current study was to investigate the role of sodium-hydrogen exchanger type 1 (NHE1) in blood brain barrier (BBB) integrity during CSD events and the contributions of this antiporter on xenobiotic uptake. Using immortalized cell lines, pharmacologic inhibition and genetic knockdown of NHE1 mitigated the paracellular uptake of radiolabeled sucrose implicating functional NHE1 in BBB maintenance. In contrast, loss of functional NHE1 in endothelial cells facilitated uptake of the anti-migraine therapeutic, sumatriptan. In female rats, cortical KCl but not aCSF selectively reduced total expression of NHE1 in cortex and PAG but increased expression in trigeminal ganglia; no changes were seen in trigeminal nucleus caudalis. Thus, in vitro observations may have a significance in vivo to increase brain sumatriptan levels. Pharmacological inhibition of NHE1 prior to cortical manipulations enhanced the efficacy of sumatriptan at early time-points but induced facial sensitivity alone. Overall, our results suggest that dysregulation of NHE1 contributes to breaches in BBB integrity, drug penetrance, and the behavioral sensitivity to the antimigraine agent, sumatriptan.
Learn More >Cannabidiol (CBD), the major non-psychoactive constituent of L., has gained traction as a potential treatment for intractable chronic pain in many conditions. Clinical evidence suggests that CBD provides therapeutic benefit in certain forms of epilepsy and imparts analgesia in certain conditions, and improves quality of life. CBD continues to be Schedule I or V on the list of controlled substances of the Drug Enforcement Agency of the United States. However, preparations labeled CBD are available publicly in stores and on the streets. However, use of CBD does not always resolve pain. CBD purchased freely entails the risk of adulteration by potentially hazardous chemicals. As well, CBD use by pregnant women is rising and poses a major health-hazard for future generations. In this mini-review, we present balanced and unbiased pre-clinical and clinical findings for the beneficial effects of CBD treatment on chronic pain and its deleterious effects on prenatal development.
Learn More >After decades of increased opioid pain reliever prescribing, providers are rapidly reducing prescribing. We hypothesized that reduced access to prescribed opioid pain relievers among patients previously reliant upon opioid pain relievers would result in increased illicit opioid use.
Learn More >As a chemotherapeutic agent, bortezomib (BTZ) is used for the treatment of multiple myeloma with adverse effect of painful peripheral neuropathy. Our current study was to determine the inhibitory effects of blocking microRNA-155 (miR-155) signal on BTZ-induced neuropathic pain and the underlying mechanisms. We employed real time RT-PCR and western blot analysis to examine the miR-155 and expression of – tumor necrosis factor-α receptor (TNFR1) in the dorsal horn of the spinal cord. Its downstream signals p38-MAPK and JNK and transient receptor potential ankyrin 1 (TRPA1) were also determined. Mechanical pain and cold sensitivity were assessed by behavioral test. In result, inhibition of miR-155 significantly attenuated mechanical allodynia and thermal hyperalgesia in BTZ rats, which was accompanied with decreasing expression of TNFR1, p38-MAPK, JNK, and TRPA1. In contrast, miRNA-155 mimics amplified TNFR1-TRPA1 pathway and augmented mechanical pain and cold sensitivity. In addition, mechanical and thermal hypersensitivity induced by miRNA-155 mimics were attenuated after blocking TNFR1, p38-MAPK, JNK, and TRPA1. Overall, we show the key role of miR-155 in modifying BTZ-induced neuropathic pain through TNFR1-TRPA1 pathway, suggesting that miR-155 is a potential target in preventing neuropathic pain development during intervention of BTZ.
Learn More >Insomnia is a major comorbid symptom of chronic pain and is likely to affect caregiver burden. This cross-sectional study investigated the association between insomnia in chronic pain patients and family caregiver burden. Participants were 60 patients with chronic pain of ≥3 months duration. Demographic and clinical information were collected using the Athens Insomnia Scale (AIS), the Pain Disability Assessment Scale (PDAS), the Hospital Anxiety and Depression Scale (HADS), and a pain intensity numerical rating scale (NRS). Family members who accompanied chronic pain patients to hospital completed the Zarit Burden Interview (ZBI). Univariate regression analysis and multiple regression analysis were conducted to clarify the associations between ZBI scores and total/subscale AIS scores. Covariates were age; sex; pain duration; and scores on the PDAS, HADS anxiety subscale, HADS depression subscale, and NRS. Insomnia was independently associated with ZBI scores [β: 0.27, 95% confidence interval (CI): 0.07-0.52, p = 0.001]. Scores on the AIS subscale of physical and mental functioning during the day were significantly associated with ZBI scores (β: 0.32, 95% CI: 0.05-0.59, p = 0.007). In conclusion, the findings suggest that in chronic pain patients, comorbid insomnia and physical and mental daytime functioning is associated with family caregiver burden independently of pain duration, pain-related disability, and pain intensity.
Learn More >The aim of this study was to validate the English version of the Itch Cognition Questionnaire in a sample of patients with chronic itch due to psoriasis or atopic dermatitis. An English-language version of an instrument assessing itch-related cognitions is needed since cognitions can contribute to a worsening of itch, and chronic itch is prevalent in English-speaking counties and internationally.
Learn More >Modern health care has brought our society innumerable benefits but has also introduced the experience of pain very early in life. For example, it is now routine care for newborns to receive various injections or have blood drawn within 24 h of life. For infants who are sick or premature, the pain experiences inherent in the required medical care are frequent and often severe, with neonates requiring intensive care admission encountering approximately fourteen painful procedures daily in the hospital. Given that much of the world has seen a steady increase in preterm births for the last several decades, an ever-growing number of babies experience multiple painful events before even leaving the hospital. These noxious events occur during a critical period of neurodevelopment when the nervous system is very vulnerable due to immaturity and neuroplasticity. Here, we provide a narrative review of the literature pertaining to the idea that early life pain has significant long-term effects on neurosensory, cognition, behavior, pain processing, and health outcomes that persist into childhood and even adulthood. We refer to clinical and pre-clinical studies investigating how early life pain impacts acute pain later in life, focusing on animal model correlates that have been used to better understand this relationship. Current knowledge around the proposed underlying mechanisms responsible for the long-lasting consequences of neonatal pain, its neurobiological and behavioral effects, and its influence on later pain states are discussed. We conclude by highlighting that another important consequence of early life pain may be the impact it has on later chronic pain states-an area of research that has received little attention.
Learn More >