Interventions to reduce meat consumption by appealing to animal welfare: Meta-analysis and evidence-based recommendations.

Reducing meat consumption may improve human health, curb environmental damage, and limit the large-scale suffering of animals raised in factory farms. Most attention to reducing consumption has focused on restructuring environments where foods are chosen or on making health or environmental appeals. However, psychological theory suggests that interventions appealing to animal welfare concerns might operate on distinct, potent pathways.

Reducing meat consumption by appealing to animal welfare: protocol for a meta-analysis and theoretical review.

Background: Reducing meat consumption may improve human health, curb environmental damage and greenhouse gas emissions, and limit the large-scale suffering of animals raised in factory farms. Previous work has begun to develop interventions to reduce individual meat consumption, often by appealing directly to individual health motivations. However, research on nutritional behavior change suggests that interventions additionally linking behavior to ethical values, identity formation, and existing social movements may be particularly effective and longer-lasting.

Open-source software for mouse-tracking in Qualtrics to measure category competition.

Mouse-tracking is a sophisticated tool for measuring rapid, dynamic cognitive processes in real time, particularly in experiments investigating competition between perceptual or cognitive categories. We provide user-friendly, open-source software ( https://osf.io/st2ef/ ) for designing and analyzing such experiments online using the Qualtrics survey platform.

Navigating a social world with robot partners: A quantitative cartography of the Uncanny Valley.

Android robots are entering human social life. However, human-robot interactions may be complicated by a hypothetical Uncanny Valley (UV) in which imperfect human-likeness provokes dislike. Previous investigations using unnaturally blended images reported inconsistent UV effects.

Accounting for the delay in the transition from acute to chronic pain: axonal and nuclear mechanisms.

Acute insults produce hyperalgesic priming, a neuroplastic change in nociceptors that markedly prolongs inflammatory mediator-induced hyperalgesia. After an acute initiating insult, there is a 72 h delay to the onset of priming, for which the underlying mechanism is unknown. We hypothesized that the delay is due to the time required for a signal to travel from the peripheral terminal to the cell body followed by a return signal to the peripheral terminal.

The fundamental unit of pain is the cell.

The molecular/genetic era has seen the discovery of a staggering number of molecules implicated in pain mechanisms [18,35,61,69,96,133,150,202,224]. This has stimulated pharmaceutical and biotechnology companies to invest billions of dollars to develop drugs that enhance or inhibit the function of many these molecules. Unfortunately this effort has provided a remarkably small return on this investment.

Role of Drp1, a key mitochondrial fission protein, in neuropathic pain.

While oxidative stress has been implicated in small-fiber painful peripheral neuropathies, antioxidants are only partially effective to treat patients. We have tested the hypothesis that Drp1 (dynamin-related protein 1), a GTPase that catalyzes the process of mitochondrial fission, which is a mechanism central for the effect and production of reactive oxygen species (ROS), plays a central role in these neuropathic pain syndromes. Intrathecal administration of oligodeoxynucleotide antisense against Drp1 produced a decrease in its expression in peripheral nerve and markedly attenuated neuropathic mechanical hyperalgesia caused by HIV/AIDS antiretroviral [ddC (2',3'-dideoxycytidine)] and anticancer (oxaliplatin) chemotherapy in male Sprague Dawley rats.

Pain and death: neurodegenerative disease mechanisms in the nociceptor.

Chronic peripheral neuropathic pain is the result of abnormal activity in sensory nerves. It is well recognized that this sensory nerve dysfunction can be caused by traumatic, toxic, or metabolic insult to the nerve. In addition, there is growing recognition that neuropathic pain is a frequent manifestation of neurodegenerative diseases.

Shared mechanisms for opioid tolerance and a transition to chronic pain.

Clinical pain conditions may remain responsive to opiate analgesics for extended periods, but such persistent acute pain can undergo a transition to an opiate-resistant chronic pain state that becomes a much more serious clinical problem. To test the hypothesis that cellular mechanisms of chronic pain in the primary afferent also contribute to the development of opiate resistance, we used a recently developed model of the transition of from acute to chronic pain, hyperalgesic priming. Repeated intradermal administration of the potent and highly selective mu-opioid agonist, [d-Ala(2),N-MePhe(4),gly-ol]-enkephalin (DAMGO), to produce tolerance for its inhibition of prostaglandin E(2) hyperalgesia, simultaneously produced hyperalgesic priming.

Participation in the decision to become vaccinated against human papillomavirus by California high school girls and the predictors of vaccine status.

Background: State and national policymakers are actively debating the merits of legally mandating the human papillomavirus (HPV) vaccine.

Methods: This was a cross-sectional pilot study designed to identify factors associated with HPV vaccination in 170 high school girls and the decision making by girls about vaccination.

Results: Overall, 48.

Critical role of nociceptor plasticity in chronic pain.

The transition from acute to chronic pain states might be the most important challenge in research to improve clinical treatment of debilitating pain. We describe a recently identified mechanism of neuronal plasticity in primary afferent nociceptive nerve fibers (nociceptors) by which an acute inflammatory insult or environmental stressor can trigger long-lasting hypersensitivity of nociceptors to inflammatory cytokines. This phenomenon, "hyperalgesic priming," depends on the epsilon isoform of protein kinase C (PKCepsilon) and a switch in intracellular signaling pathways that mediate cytokine-induced nociceptor hyperexcitability.

Neurotoxic catecholamine metabolite in nociceptors contributes to painful peripheral neuropathy.

The neurotoxic effects of catecholamine metabolites have been implicated in neurodegenerative diseases. As some sensory neurons express tyrosine hydroxylase and monoamine oxidase (MAO), we investigated the potential contribution of catecholamine metabolites to neuropathic pain in a model of alcoholic neuropathy. The presence of catecholamines in sensory neurons is supported by capsaicin-stimulated epinephrine release, an effect enhanced in ethanol-fed rats.

Stress induces a switch of intracellular signaling in sensory neurons in a model of generalized pain.

Stress dramatically exacerbates pain in diseases such as fibromyalgia and rheumatoid arthritis, but the underlying mechanisms are unknown. We tested the hypothesis that stress causes generalized hyperalgesia by enhancing pronociceptive effects of immune mediators. Rats exposed to nonhabituating sound stress exhibited no change in mechanical nociceptive threshold, but showed a marked increase in hyperalgesia evoked by local injections of prostaglandin E(2) or epinephrine.

Interaction of transient receptor potential vanilloid 4, integrin, and SRC tyrosine kinase in mechanical hyperalgesia.

Although the transient receptor potential vanilloid 4 (TRPV4) has been implicated in the process of osmomechanical transduction, it appears to make little contribution to the normal somatosensory detection of mechanical stimuli. However, evidence suggests that it may play an important role in mechanical hyperalgesia. In the present study, we examined the common requirement for TRPV4 in mechanical hyperalgesia associated with diverse pain models and investigated whether the very close association observed between TRPV4 and mechanical hyperalgesia, regardless of etiology, reflects a close functional connection of TRPV4 with other molecules implicated in mechanical transduction.

A transient receptor potential vanilloid 4-dependent mechanism of hyperalgesia is engaged by concerted action of inflammatory mediators.

The transient receptor potential vanilloid 4 (TRPV4) is a primary afferent transducer that plays a crucial role in neuropathic hyperalgesia for osmotic and mechanical stimuli, as well as in inflammatory mediator-induced hyperalgesia for osmotic stimuli. In view of the clinical importance of mechanical hyperalgesia in inflammatory states, the present study investigated the role of TRPV4 in mechanical hyperalgesia induced by inflammatory mediators and the second-messenger pathways involved. Intradermal injection of either the inflammogen carrageenan or a soup of inflammatory mediators enhanced the nocifensive paw-withdrawal reflex elicited by hypotonic or mechanical stimuli in rat.

Fibromyalgia: the nerve of that disease.

Fibromyalgia syndrome (FM) is a common, often debilitating and intractable, chronic, generalized pain condition. The development of effective therapies to treat FM has been hindered by a lack of understanding of fundamental mechanisms in the etiology of FM. In view of prominent characteristics that FM shares with other generalized pain conditions, we suggest that a key mechanism in such disorders may be that of altered activity in the subdiaphragmatic vagus nerve.

Primary afferent second messenger cascades interact with specific integrin subunits in producing inflammatory hyperalgesia.

We recently reported that hyperalgesia induced by the inflammatory mediator prostaglandin E(2) (PGE(2)) requires intact alpha1, alpha3 and beta1 integrin subunit function, whereas epinephrine-induced hyperalgesia depends on alpha5 and beta1. PGE(2)-induced hyperalgesia is mediated by protein kinase A (PKA), while epinephrine-induced hyperalgesia is mediated by a combination of PKA, protein kinase Cepsilon (PKCepsilon) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK). We hypothesized that inflammatory mediator-induced hyperalgesia involves specific interactions between different subsets of integrin subunits and particular second messenger species.

Chronic hyperalgesic priming in the rat involves a novel interaction between cAMP and PKCepsilon second messenger pathways.

Toward the goal of defining new pharmacological targets for the treatment of chronic pain conditions, in previous studies we established a model, termed 'hyperalgesic priming,' in which an acute inflammatory stimulus causes a long-lasting latent susceptibility to hyperalgesia induced by subsequent exposures to the inflammatory mediator, prostaglandin E2 (PGE2). Those investigations suggested the hypothesis that priming induces a novel linkage between the PGE2-activated second messenger cascade and the epsilon isoform of protein kinase C (PKCepsilon). In the present study, comparison of dose-response relations for hyperalgesia produced by PGE2, forskolin, 8-Br-cAMP, or the protein kinase A (PKA) catalytic subunit, in primed versus normal animals, demonstrated that priming-induced enhancement of the PGE2-activated second messenger cascade occurs downstream to adenylate cyclase and upstream to PKA.

Transient receptor potential vanilloid 4 is essential in chemotherapy-induced neuropathic pain in the rat.

The development of treatments for neuropathic pain has been hindered by our limited understanding of the basic mechanisms underlying abnormalities in nociceptor hyperexcitability. We recently showed that the polymodal receptor transient receptor potential vanilloid 4 (TRPV4), a member of the transient receptor potential (TRP) family of ion channels, may play a role in inflammatory pain (Alessandri-Haber et al., 2003).

Hypotonicity induces TRPV4-mediated nociception in rat.

We hypothesized that TRPV4, a member of the transient receptor family of ion channels, functions as a sensory transducer for osmotic stimulus-induced nociception. We found that, as expected for a transducer molecule, TRPV4 protein is transported in sensory nerve distally toward the peripheral nerve endings. In vivo single-fiber recordings in rat showed that hypotonic solution activated 54% of C-fibers, an effect enhanced by the hyperalgesic inflammatory mediator prostaglandin E2.

Transient attenuation of protein kinase Cepsilon can terminate a chronic hyperalgesic state in the rat.

Recently we demonstrated that a single 3-day episode of carrageenan-induced acute cutaneous inflammation can create a chronic state of increased susceptibility to inflammatory hyperalgesia. In this latent "primed" state, although there is no ongoing hyperalgesia, the hyperalgesic response to subsequent challenges with inflammatory agent (prostaglandin E2; PGE2) is greatly enhanced. Furthermore, the PGE2-induced hyperalgesia in primed skin was found to require activity of the epsilon isozyme of protein kinase C (PKCepsilon), a second messenger that is not required for PGE2-induced hyperalgesia in control animals.

Fasting is a physiological stimulus of vagus-mediated enhancement of nociception in the female rat.

The vagus nerve modulates nociception by a mechanism dependent upon gonadal hormones and the adrenal medulla. In the present study we tested the hypothesis that this modulation is dynamically controlled by physiological stimulation of structures innervated by the subdiaphragmatic vagus. Specifically, food deprivation (fasting) was employed to increase activity in the subdiaphragmatic vagus, and the experiments were performed mainly in female rats because our previous observations suggested that baseline activity in the pathway is lower in females than in males.

Altered temporal pattern of evoked afferent activity in a rat model of vincristine-induced painful peripheral neuropathy.

It is known that the level of activity in nociceptive primary afferent nerve fibers increases in neuropathic conditions that produce pain, but changes in the temporal patterning of action potentials have not been analyzed in any detail. Because the patterning of action potentials in sensory nerve fibers might play a role in the development of pathological pain states, we studied patterning of mechanical stimulus-evoked action potential trains in nociceptive primary afferents in a rat model of vincristine-induced painful peripheral neuropathy. Systemic administration of vincristine (100 microg/kg) caused approximately half the C-fiber nociceptors to become markedly hyperresponsive to mechanical stimulation.

Bradykinin-12-lipoxygenase-VR1 signaling pathway for inflammatory hyperalgesia.

The capsaicin-sensitive vanilloid receptor (VR1) was recently shown to play an important role in inflammatory pain (hyperalgesia), but the underlying mechanism is unknown. We hypothesized that pain-producing inflammatory mediators activate capsaicin receptors by inducing the production of fatty acid agonists of VR1. This study demonstrates that bradykinin, acting at B2 bradykinin receptors, excites sensory nerve endings by activating capsaicin receptors via production of 12-lipoxygenase metabolites of arachidonic acid.

Role of protein kinase Cepsilon and protein kinase A in a model of paclitaxel-induced painful peripheral neuropathy in the rat.

The clinical use of the antineoplastic agent paclitaxel (Taxol) is significantly limited in its effectiveness by a dose-related painful peripheral neuropathy. To evaluate underlying mechanisms, we developed a model of Taxol-induced painful peripheral neuropathy in the rat and determined the involvement of two second messengers that contribute to enhanced nociception in other models of inflammatory and neuropathic pain, protein kinase Cepsilon and protein kinase A. Taxol administered acutely, or chronically over 12 days, produced a decrease in mechanical nociceptive threshold.