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Preemptive analgesia encompasses different perioperative interventions that have the final aim of decreasing postoperative pain and improving recovery. Recently, peripheral analgesic effects of oxytocinergic modulation have been suggested. In this regard, we tested the potential analgesic effects of subcutaneous oxytocin (OT) infiltration in patients submitted to laparoscopic cholecystectomy.
Learn More >Back pain is the leading cause of disability worldwide and contributes to significant socioeconomic impacts worldwide. It has been hypothesized that the degenerative intervertebral disc (IVD) contributes to back pain by sensitizing nociceptive neurons innervating the IVD to stimuli that would not be painful to healthy patients; however, the inflammatory signaling networks mediating this sensitization remain poorly understood. A better understanding of the underlying mechanisms of degenerative IVD induced changes in nociception are required to improve our understanding and treatment of back pain. Towards these ends, we developed a novel in vitro model to investigate degenerative IVD induced changes in dorsal root ganglion (DRG) neuron activation by measuring DRG neuron activity following neuron seeding on human degenerative IVD tissue collected from patients undergoing surgical treatment for back pain. Lentiviral CRISPR epigenome editing vectors were built to down-regulate the inflammatory receptors TNFR1, IL1R1, and IL6st in DRG neurons in single-plex and multi-plex. Multiplex CRISPR epigenome editing of inflammatory receptors demonstrated that degenerative IVD tissue drives thermal sensitization through the simultaneous and redundant signaling of IL-6, TNF-α, and IL-1β. This work elucidates redundant signaling pathways in neuron interactions with the degenerative IVD and suggests the need for multiplex targeting of IL-6, TNF-α, and IL-1β for pain modulation in the degenerative IVD.
Learn More >The objective of this investigation was to examine the distribution of galcanezumab and a control immunoglobulin 4 antibody containing the same constant regions as galcanezumab, into peripheral and central tissues.
Learn More >Excessive prescription of opioids has become a national problem. Providers must attempt to decrease the amount of opioids prescribed while still providing patients with adequate pain relief after surgery.
Learn More >As opioid abuse and addiction have developed into a major national health crisis, prescription of opioids for pain management has become more controversial. However, opioids do help some patients by providing pain relief and improving the quality of life. To better understand the addictive properties of opioids under chronic pain conditions, we used a conditioned place preference (CPP) paradigm to examine the rewarding properties of morphine in rats with persistent nociception.
Learn More >Calcitonin gene-related peptide has emerged as a therapeutic target in migraine. Monoclonal antibodies and small molecule receptor antagonists (gepants) directed against CGRP have been approved or are in Phase II or III clinical trials. For monitoring the long-term safety of these drugs, it is helpful to consider the role of CGRP in brain functioning.
Learn More >It is expected that the number of surgical procedures to diagnose, treat, and palliate cancers will increase in the near future. While many of those interventions can be performed with minimally invasive techniques, others require surgical large incisions and in some instances, they involve multiple areas of the body (i.e., tumor resections with flap reconstructions). Pain after major oncological procedures can be severe and many times difficult to treat as patients can present to the operating room with several conditions including preoperative pain (i.e., rapidly growing tumors and painful neuropathies), opioid tolerance, and contraindications to nonopioid analgesics or regional anesthesia. Inadequately treated postoperative pain is associated with activation of the sympathetic system, postoperative complications, large perioperative opioid use, and an increased risk of developing postoperative persistent pain. Furthermore, it has been theorized that poorly treated pain is associated with cancer recurrence and a reduced survival. Lastly, recent research questions the oncological safety of robotic surgery in gynecological procedures and indicates the need of open surgeries, which will be associated with an increased risk in moderate-to-severe postoperative pain. In conclusion, the management of acute postoperative pain in patients with cancer can be challenging.
Learn More >To use clustering analysis of patient symptoms to discover common patient subtypes in females and males with interstitial cystitis/bladder pain syndrome (IC/BPS) or chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).
Learn More >The host evolves redundant mechanisms to preserve physiological processing and homeostasis. These functions range from sensing internal and external threats, creating a memory of the insult and generating reflexes which aim to resolve inflammation. Impairment in such functioning leads to chronic inflammatory diseases. By interacting through a common language of ligands and receptors, the immune and sensory nervous systems work in concert to accomplish such protective functions. While this bidirectional communication helps to protect from danger, it can contribute to disease pathophysiology. Thus, the somatosensory nervous system is anatomically positioned within primary and secondary lymphoid tissues and mucosa to modulate immunity directly. Upstream of this interplay, neurons detect danger which prompts the release of neuropeptides initiating i) defensive reflexes (ranging from withdrawal response to coughing); and ii) chemotaxis, adhesion and local infiltration of immune cells. The resulting outcome of such neuro-immune interplay is still ill-defined, but consensual findings start to emerge and support neuropeptides as blockers of T 1-mediated immunity but also as drivers of T 2 immune responses. However, the modalities detected by nociceptors revealed broader than mechanical pressure and temperature sensing and include signals as various as cytokines and pathogens to immunoglobulins and even microRNAs. Along these lines, we aggregated various dorsal root ganglion sensory neurons expression profiling datasets supporting such wide-ranging sensing capabilities and to help identify novel danger detection modalities of these cells. Thus, revealing unexpected aspects of nociceptor neurons biology might prompt the identification of novel drivers of immunity, means to resolve inflammation and strategies to safeguard homeostasis. This article is protected by copyright. All rights reserved.
Learn More >Supportive touch has remarkable benefits in childbirth and during painful medical procedures. But does social touch influence pain neurophysiology, ie, the brain processes linked to nociception and primary pain experience? What other brain processes beyond primary pain systems mediate their analgesic effects? In this study, women (N = 30) experienced thermal pain while holding their romantic partner's hand or an inert device. Social touch reduced pain and attenuated functional magnetic resonance imaging activity in the Neurologic Pain Signature (NPS)-a multivariate brain pattern sensitive and specific to somatic pain-and increased connectivity between the NPS and both somatosensory and "default mode" regions. Brain correlates of touch-induced analgesia included reduced pain-related activation in (1) regions targeted by primary nociceptive afferents (eg, posterior insula, and anterior cingulate cortex); and (b) regions associated with affective value (orbitofrontal cortex), meaning (ventromedial prefrontal cortex [PFC]), and attentional regulation (dorsolateral PFC). Activation reductions during handholding (vs holding a rubber device) significantly mediated reductions in pain intensity and unpleasantness; greater pain reductions during handholding correlated with greater increases in emotional comfort, which correlated with higher perceived relationship quality and (a trend toward) greater perceived closeness with the romantic partner. The strongest mediators of analgesia were activity reductions in a brain circuit traditionally associated with stress and defensive behavior in mammals, including ventromedial and dorsomedial PFC, rostral anterior cingulate cortex, amygdala/hippocampus, hypothalamus, and periaqueductal gray matter. Social touch affects core brain processes that contribute to pain and pain-related affective distress in females, and should be considered alongside other treatments in medical and caregiving contexts.
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