Making a Case for Whole Person Health.

Our conventional approach to health care tends to separate patients' health by body system, treating each independently and "efficiently"-e.g., minimal time with a provider, reliance on medications, and little investment to support behavioral and lifestyle improvements.

Complementary and integrative health therapies in whole person resilience research.

Complementary and integrative health approaches can improve health and well-being, as well as play an important role in disease prevention. The concept of whole person health builds on these concepts by empowering individuals, families, communities, and populations to improve their health in multiple interconnected domains: biological, behavioural, social, and environmental. Research on whole person health involves studies of interconnected biological systems and complex approaches to prevention and treatment.

Biochemical and behavioral effects of decreasing dietary linoleic acid and increasing eicosapentaenoic acid and docosahexaenoic acid in a rat chronic monoarthrits model.

Clinical studies have demonstrated that decreasing linoleic acid (LA) while increasing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in diets evokes an analgesic effect in headache sufferers. We utilized a rat chronic monoarthritis model to determine if these analgesic effects can be reproduced in rats and to and further probe potential analgesic mechanisms. We fed 8 rats a control diet (with fatty acid levels similar to standard US diets) and 8 rats a low LA diet with added EPA and DHA (H3L6 diet) and after 10 weeks, performed a unilateral intraarticular injection of Complete's Freund Adjuvant (CFA).

Innocuous pressure sensation requires A-type afferents but not functional ΡΙΕΖΟ2 channels in humans.

The sensation of pressure allows us to feel sustained compression and body strain. While our understanding of cutaneous touch has grown significantly in recent years, how deep tissue sensations are detected remains less clear. Here, we use quantitative sensory evaluations of patients with rare sensory disorders, as well as nerve blocks in typical individuals, to probe the neural and genetic mechanisms for detecting non-painful pressure.

Persistent inflammatory pain alters sexually-motivated behavior in male rats.

Urine from pro-œstrus female rodents evokes increased levels of sexually-motivated behaviors in males, including sniffing and scent marking of the urine spot as well as activation of brain reward regions. Stressors such as social defeat can adversely impact urine scent marking behavior in male rodents, an effect that can be mitigated with anti-depressant drugs. Persistent pain is also known to be a potent stressor, producing elevated levels of plasma corticosterone as well as reduced sucrose preference and reduced social interaction.

Prevalence and Profile of High-Impact Chronic Pain in the United States.

The multidimensional nature of chronic pain is not reflected by definitions based solely on pain duration, resulting in high prevalence estimates limiting effective policy development. The newly proposed concept of high-impact chronic pain (HICP) incorporates both disability and pain duration to identify a more severely impacted portion of the chronic pain population yet remains uncharacterized at the population level. As such, we used the 2011 National Health Interview Survey (N = 15,670) to 1) assess the likelihood of disability in the overall chronic pain population, 2) estimate the prevalence of HICP, and 3) characterize the disability, health status, and health care use profile of this population in the United States.

The Impact of Exercise in Rodent Models of Chronic Pain.

Purpose Of Review: Physical activity is increasingly recommended for chronic pain. In this review, we briefly survey recent, high-quality meta-analyses on the effects of exercise in human chronic pain populations, followed by a critical discussion of the rodent literature.

Recent Findings: Most meta-analytical studies on the effects of exercise in human chronic pain populations describe moderate improvements in various types of chronic pain, despite substantial variability in the outcomes reported in the primary literature.

Chronic neuropathic pain reduces opioid receptor availability with associated anhedonia in rat.

The opioid system plays a critical role in both the experience and management of pain. Although acute activation of the opioid system can lead to pain relief, the effects of chronic pain on the opioid system remain opaque. Cross-sectional positron emission tomography (PET) studies show reduced availability of brain opioid receptors in patients with chronic pain but are unable to (1) determine whether these changes are due to the chronic pain itself or due to preexisting or medication-induced differences in the endogenous opioid system, and (2) identify the neurobiological substrate of reduced opioid receptor availability.

Comment on "Molecular and neural basis of contagious itch behavior in mice".

Yu (Reports, 10 March 2017, p. 1072) state that contagious itch occurs in mice based on imitative scratching in normal mice observing excessive scratching in genetically modified demonstrator mice. However, despite employing multiple behavioral analysis approaches, we were unable to extend these findings to normal mice observing the well-established histamine model of acute itch in demonstrator mice.

Mild Social Stress in Mice Produces Opioid-Mediated Analgesia in Visceral but Not Somatic Pain States.

Unlabelled: Visceral pain has a greater emotional component than somatic pain. To determine if the stress-induced analgesic response is differentially expressed in visceral versus somatic pain states, we studied the effects of a mild social stressor in either acute visceral or somatic pain states in mice. We show that the presence of an unfamiliar conspecific mouse (stranger) in an adjacent cubicle of a standard transparent observation box produced elevated plasma corticosterone levels compared with mice tested alone, suggesting that the mere presence of a stranger is stressful.

Modest Amounts of Voluntary Exercise Reduce Pain- and Stress-Related Outcomes in a Rat Model of Persistent Hind Limb Inflammation.

Unlabelled: Aerobic exercise improves outcomes in a variety of chronic health conditions, yet the support for exercise-induced effects on chronic pain in humans is mixed. Although many rodent studies have examined the effects of exercise on persistent hypersensitivity, the most used forced exercise paradigms that are known to be highly stressful. Because stress can also produce analgesic effects, we studied how voluntary exercise, known to reduce stress in healthy subjects, alters hypersensitivity, stress, and swelling in a rat model of persistent hind paw inflammation.

eIF2α phosphorylation controls thermal nociception.

A response to environmental stress is critical to alleviate cellular injury and maintain cellular homeostasis. Eukaryotic initiation factor 2 (eIF2) is a key integrator of cellular stress responses and an important regulator of mRNA translation. Diverse stress signals lead to the phosphorylation of the α subunit of eIF2 (Ser51), resulting in inhibition of global protein synthesis while promoting expression of proteins that mediate cell adaptation to stress.

Restraint training for awake functional brain scanning of rodents can cause long-lasting changes in pain and stress responses.

With the increased interest in longitudinal brain imaging of awake rodents, it is important to understand both the short-term and long-term effects of restraint on sensory and emotional processing in the brain. To understand the effects of repeated restraint on pain behaviors and stress responses, we modeled a restraint protocol similar to those used to habituate rodents for magnetic resonance imaging scanning, and studied sensory sensitivity and stress hormone responses over 5 days. To uncover lasting effects of training, we also looked at responses to the formalin pain test 2 weeks later.

Translational control of nociception via 4E-binding protein 1.

Activation of the mechanistic/mammalian target of rapamycin (mTOR) kinase in models of acute and chronic pain is strongly implicated in mediating enhanced translation and hyperalgesia. However, the molecular mechanisms by which mTOR regulates nociception remain unclear. Here we show that deletion of the eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), a major mTOR downstream effector, which represses eIF4E activity and cap-dependent translation, leads to mechanical, but not thermal pain hypersensitivity.

Stimulation of cutaneous low threshold mechanoreceptors in mice after intracolonic capsaicin increases spinal c-Fos labeling in an NKCC1-dependent fashion.

Unlabelled: Stimulation of peripheral nociceptors results in increased c-Fos labeling in spinal cord regions associated with nociceptive processing. Accordingly, intracolonic capsaicin, which generates robust secondary (referred) allodynia on the abdomen of mice, also causes an increased spinal c-Fos labeling. In naïve rodents, low intensity innocuous stimulation does not affect c-Fos labeling in spinal nociceptive regions.

PKMζ is essential for spinal plasticity underlying the maintenance of persistent pain.

Background: Chronic pain occurs when normally protective acute pain becomes pathologically persistent. We examined here whether an isoform of protein kinase C (PKC), PKMζ, that underlies long-term memory storage in various brain regions, also sustains nociceptive plasticity in spinal cord dorsal horn (SCDH) mediating persistent pain.

Results: Cutaneous injury or spinal stimulation produced persistent increases of PKMζ, but not other atypical PKCs in SCDH.

Role of the NKCC1 co-transporter in sensitization of spinal nociceptive neurons.

The Na(+), K(+), 2Cl(-) co-transporter type 1 (NKCC1) plays a pivotal role in hyperalgesia associated with inflammatory stimuli. NKCC1 contributes to maintain high [Cl(-)](i) in dorsal root ganglia (DRG) neurons which cause primary afferent depolarization (PAD) when GABA(A) receptors are activated. Enhanced GABA-induced depolarization, through increased NKCC1 activity, has been hypothesized to produce orthodromic spike activity of sufficient intensity to account for touch-induced pain.

Effects of inflammation on the ultrastructural localization of spinal cord dorsal horn group I metabotropic glutamate receptors.

Inflammatory pain is thought to induce functional plasticity of spinal dorsal horn neurons and may produce changes in glutamate receptor expression. Plasticity of group I metabotropic glutamate receptors (mGluR1 and mGluR5) is important in various neuronal systems, and these receptors are also known to modulate nociceptive neurotransmission in the spinal dorsal horn. The present study aimed at determining whether persistent inflammatory pain produces alterations in intracellular and plasma membrane-associated mGluR1alpha and mGluR5 in spinal cord dorsal horn.

Spinal NKCC1 blockade inhibits TRPV1-dependent referred allodynia.

Background: The Na+, K+, 2Cl- type I cotransporter (NKCC1) and TRPV1 receptors, at the level of the dorsal horn, have been implicated in mediating allodynia in response to an inflammatory insult. The NKCC1 cotransporter regulates intracellular [Cl-] and thus the magnitude and polarity of GABAA receptor responses in neurons. TRPV1 receptors transduce diverse chemical and natural stimuli in nociceptors and are critical for inflammatory hyperalgesia.