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Pruritus, a common symptom of psoriasis, negatively impacts quality of life; however, treatment of lesional skin does not consistently alleviate psoriatic itch.
Learn More >Astrocytes are essential contributors to neuronal function. As a consequence, disturbed astrocyte-neuron interactions are involved in the pathophysiology of several neurological disorders, with a strong impact on brain circuits and behavior. Here, we describe altered cortical physiology in a genetic mouse model of familial hemiplegic migraine type 2 (FHM2), with reduced expression of astrocytic Na,K-ATPases. We used whole-cell electrophysiology, two-photon microscopy, and astrocyte gene rescue to demonstrate that an impairment in astrocytic glutamate uptake promotes NMDA spike generation in dendrites of cingulate cortex pyramidal neurons and enhances output firing of these neurons. Astrocyte compensation of the defective ATPase in the cingulate cortex rescued glutamate uptake, prevented abnormal NMDA spikes, and reduced sensitivity to cranial pain triggers. Together, our results demonstrate that impaired astrocyte function alters neuronal activity in the cingulate cortex and facilitates migraine-like cranial pain states in a mouse model of migraine.
Learn More >Chronic pain is common in children and increases their risk for developing a chronic pain condition in adulthood, yet relatively little is known about early parental psychosocial factors that predict the development of chronic pain in childhood. We examined the extent to which chronic pain frequency in a community sample of 6-year-old children was related to frequency of chronic pain in their parents, and was prospectively predicted by early maternal risk (i.e., depressive symptoms) and promotive (i.e., hope) factors. Fifty primary caregivers (94% mothers) of 6-year-old twin children who were enrolled in a larger study during children's infancy were randomly selected to complete a telephone interview regarding their own, their partner's, and their children's pain symptoms and functioning. Pain symptom scores were derived by summing the number of seven possible body areas that were painful at least monthly during the prior 6 months. Pain symptoms at three or more sites were coded as multisite pain. Prior maternal depressive symptoms and hope were assessed when children were aged 12-months. Pain symptom scores were positively correlated within families, and risk of child pain increased in a dose-response fashion according to whether neither, one, or both parents experienced multisite pain. Maternal hope but not depressive symptoms prospectively predicted fewer painful body regions in children five years later. Findings suggest that pain runs in families and pain in childhood may be influenced by early maternal psychosocial factors. Future research should focus on how parents' own health and psychological attributes influence risk for children's chronic pain.
Learn More >Low back pain (LBP) is prevalent and may transition into chronic LBP (cLBP) with associated reduced quality of life, pain, and disability. Because cLBP affects a heterogenous population, rehabilitation efforts must be individualized to meet the needs of various patient populations as well as individuals. This narrative review evaluated the many approaches to LBP rehabilitation including treatment-based classifications and specific types of rehabilitation efforts from exercise and physical therapy to spinal manipulation and bracing. Clinicians caring for patients with LBP or cLBP must be aware of the various options to find the right treatment course for each patient. In many cases, with proper patient expectations and care, nonpharmacological options may suffice to manage cLBP. While there is a rightful role for analgesics in the management of LBP, nonpharmacological options should be seriously considered, as they can play an important and health-sustaining role in patient management.
Learn More >Postherpetic neuralgia (PHN) is one of the most common complications of herpes zoster (HZ). Heritable factors have been found to play a role in various clinical pain symptoms. However, the effect of gene variability on the susceptibility of PHN remains poorly understood.
Learn More >Patients undergoing cancer treatment often experience chemotherapy-induced neuropathic pain at their extremities, for which there is no U.S. Food and Drug Administration-approved drug. The authors hypothesized that local sympathetic blockade, which is used in the clinic to treat various pain conditions, can also be effective to treat chemotherapy-induced neuropathic pain.
Learn More >Sodium channel Nav1.7, encoded by the SCN9A gene, is a well-validated target that plays a key role in controlling pain sensation. Loss-of-function mutations of Nav1.7 can cause a syndrome of profound congenital insensitivity to pain in humans. Better understanding of how the loss of Nav1.7 leads to loss of pain sensibility would help to decipher the fundamental mechanisms of nociception and inform strategies for development of novel analgesics. Using a recently described rat Nav1.7 loss-of-function model with deficient nociception but intact olfactory function, we investigated the involvement of endogenous opioid and cannabinoid systems in this rodent model of Nav1.7-related congenital insensitivity to pain. We found that both the opioid receptor antagonist naloxone and cannabinoid receptor blockers SR141716A (rimonabant) and SR144528 fail to restore acute pain sensitivity in Nav1.7 loss-of-function rats. We observed, however, that after rimonabant administration, Nav1.7 loss-of-function but not WT rats displayed abnormal behaviours, such as enhanced scratching, caudal self-biting, and altered facial expressions; the underlying mechanism is still unclear. Dorsal root ganglion neurons from Nav1.7 loss-of-function rats, although hypoexcitable compared with WT neurons, were still able to generate action potentials in response to noxious heat and capsaicin. Our data indicate that complete loss of dorsal root ganglion neuron excitability is not required for insensitivity to pain and suggest that endogenous opioid and cannabinoid systems are not required for insensitivity to pain in the absence of Nav1.7 channels in this rat Nav1.7 loss-of-function model.
Learn More >Sickle cell disease (SCD) is a genetic disorder characterized by hemolysis, end-organ damage, inflammation, and pain. Recurrent and unpredictable episodes of acute pain due to vaso-occlusive crises are a unique feature of SCD. Many patients also develop lifelong chronic pain. Opioids are the primary method of pain treatment in SCD; however, continued use is associated with several adverse effects. Integrative approaches to treating pain in SCD are increasingly being explored to prevent the side effects associated with opioids. In this review, we highlight the mechanisms of pain in SCD and describe mechanism-based integrative approaches for treating pain.
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