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The lack of sensitive and robust behavioral assessments of pain in preclinical models has been a major limitation for both pain research and the development of novel analgesics. Here we demonstrate a novel data acquisition and analysis platform that provides automated, quantitative, and objective measures of naturalistic rodent behavior in an observer-independent and unbiased fashion. The technology records freely-behaving mice, in the dark, over extended periods for continuous acquisition of two parallel video data streams: 1) near-infrared frustrated total internal reflection (FTIR) for detecting the degree, force and timing of surface contact, and 2) simultaneous ongoing video-graphing of whole-body pose. Using machine vision and machine learning we automatically extract and quantify behavioral features from these data to reveal moment-by-moment changes that capture the internal pain state of rodents in multiple pain models. We show that these voluntary pain-related behaviors are reversible by analgesics and that analgesia can be automatically and objectively differentiated from sedation. Finally, we used this approach to generate a paw luminance ratio measure that is sensitive in capturing dynamic mechanical hypersensitivity over a period of time and scalable for high-throughput pre-clinical analgesic efficacy assessment.
Learn More >Neurons in the superficial dorsal horn that express the gastrin-releasing peptide receptor (GRPR) are strongly implicated in spinal itch pathways. However, a recent study reported that many of these correspond to vertical cells, a population of interneurons that are thought to transmit nociceptive information. In this study, we have used a GRPRCreERT2 mouse line to identify and target cells that possess Grpr mRNA. We find that the GRPR cells are highly concentrated in lamina I and the outer part of lamina II, that they are all glutamatergic, and that they account for ∼15% of the excitatory neurons in the superficial dorsal horn. We had previously identified 6 neurochemically distinct excitatory interneuron populations in this region based on neuropeptide expression and the GRPR cells are largely separate from these, although they show some overlap with cells that express substance P. Anatomical analysis revealed that the GRPR neurons are indeed vertical cells, and that their axons target each other, as well as arborising in regions that contain projection neurons: lamina I, the lateral spinal nucleus and the lateral part of lamina V. Surprisingly, given the proposed role of GRPR cells in itch, we found that most of the cells received monosynaptic input from Trpv1-expressing (nociceptive) afferents, that the great majority responded to noxious and pruritic stimuli, and that chemogenetically activating them resulted in pain- and itch-related behaviours. Together, these findings suggest that the GRPR cells are involved in spinal cord circuits that underlie both pain and itch.
Learn More >Tanezumab is a monoclonal antibody against nerve growth factor that is under investigation for the treatment of osteoarthritis (OA) pain. We conducted subgroup analyses of two randomized phase 3 studies to summarize efficacy, general safety, and adjudicated joint safety of tanezumab in Japanese patients with moderate-to-severe OA.
Learn More >The neural mechanisms underlying placebo analgesia have attracted considerable attention over the recent years. In contrast, little is known about the neural underpinnings of a nocebo-induced increase in pain. We previously showed that nocebo-induced hyperalgesia is accompanied by increased activity in the hippocampus that scaled with the perceived level of anxiety. As a key node of the neural circuitry of perceived threat and fear, the hippocampus has recently been proposed to coordinate defensive behaviour in a context-dependent manner. Such a role requires close interactions with other regions involved in the detection of and responses to threat. Here, we investigated the functional connectivity of the hippocampus during nocebo-induced hyperalgesia. Our results show an increase in functional connectivity between hippocampus and brain regions implicated in the processing of sensory-discriminative aspects of pain (posterior insula and primary somatosensory/motor cortex) as well as the periaqueductal gray (PAG). This nocebo-induced increase in connectivity scaled with an individual's increase in anxiety. Moreover, hippocampus connectivity with the amygdala was negatively correlated with the pain intensity reported during nocebo hyperalgesia relative to the placebo condition. Our findings suggest that the hippocampus links nocebo-induced anxiety to a heightened responsiveness to nociceptive input through changes in its crosstalk with pain-modulatory brain areas.
Learn More >Virtual reality (VR) is a computer technology that immerses a user in a completely different reality. The application of VR in acute pain settings is well established. However, in chronic pain, the applications and outcome parameters influenced by VR are less clear.
Learn More >The aim of this review is to aid in choosing safe options when assessing potential risks of acute migraine treatments based on known mechanisms of action and anticipated safety concerns.
Learn More >Chronic low back pain (LBP), neck pain (NP), and sleep quality (SQ) are genetically influenced. All three conditions frequently co-occur and shared genetic etiology on a pairwise base has been reported. However, to our knowledge no study has yet investigated if these three conditions are influenced by the same genetic and environmental factors and the extent and pattern of genetic overlap between them, hence the current research.
Learn More >Growing evidence demonstrates the benefit of Acceptance and Commitment Therapy (ACT) for people with chronic pain. However, there remain people with chronic pain who do not benefit from ACT, and predicting treatment response is difficult.
Learn More >To review data for bupivacaine/meloxicam extended-release (ER) solution for management of postoperative pain and opioid-sparing effects.
Learn More >Offset analgesia (OA) is characterized by a disproportionately large reduction in pain following a small decrease in noxious stimulation and is based on temporal pain contrast enhancement (TPCE). The underlying mechanisms of this phenomenon are still poorly understood. This study is aiming to investigate whether TPCE can also be induced by repetitive stimulation, i.e., by stimuli clearly separated in time.
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