SDIMMMER: A Proposed Clinical Approach to Optimize Cellular Physiology in Regenerative Medicine.

SDIMMMER is an acronym intended for use in both clinical practice and medical research. It facilitates a comprehensive evaluation of a patient's metabolic profile and serves as a mnemonic for the following key assessment areas: Sleep, Diet, Microbiome, Metabolism, Medications, Exams, and Rehabilitation. In the clinical setting, SDIMMMER's primary objective is to monitor and manage the patient's metabolic status, particularly targeting low-grade chronic systemic inflammation, a hallmark of metabolic syndrome (MS).

The Implications of Brain-Derived Neurotrophic Factor in the Biological Activities of Platelet-Rich Plasma.

Platelet-rich plasma (PRP) is a biological blood-derived therapeutic obtained from whole blood that contains higher levels of platelets. PRP has been primarily used to mitigate joint degeneration and chronic pain in osteoarthritis (OA). This clinical applicability is based mechanistically on the release of several proteins by platelets that can restore joint homeostasis.

The Biological Role of Platelet Derivatives in Regenerative Aesthetics.

Bioproducts derived from platelets have been extensively used across various medical fields, with a recent notable surge in their application in dermatology and aesthetic procedures. These products, such as platelet-rich plasma (PRP) and platelet-rich fibrin (PRF), play crucial roles in inducing blood vessel proliferation through growth factors derived from peripheral blood. PRP and PRF, in particular, facilitate fibrin polymerization, creating a robust structure that serves as a reservoir for numerous growth factors.

Intraarticular monomethyl fumarate as a perspective therapy for osteoarthritis by macrophage polarization.

Background: Osteoarthritis (OA) is a chronic disease that may lead to joint structure degeneration, cartilage destruction, osteophyte formation, subchondral bone disruption, and pain. In this scenario, a higher proportion of the proinflammatory macrophage type 1 (M1) than the anti-inflammatory macrophage type 2 (M2) could be highlighted as a hallmark of OA progression. The balance between these two macrophage types emerges as a new therapeutic target in OA.

Effect of propranolol on temporomandibular joint pain in repeatedly stressed rats.

Stress substantially increases the risk of developing painful temporomandibular disorders (TMDs) by influencing the release of endogenous catecholamines. Propranolol, an antagonist of β-adrenergic receptors, has shown potential in alleviating TMD-associated pain, particularly when the level of catecholamines is elevated. The aim of this study was to explore whether intra-articular propranolol administration is effective in diminishing temporomandibular joint (TMJ) pain during repeated stress situations.

Effect of sound-induced repeated stress on the development of pain and inflammation in the temporomandibular joint of female and male rats.

Temporomandibular disorder (TMD) is a common painful condition of the temporomandibular joint (TMJ) and associated structures. Stress is a significant risk factor for developing this painful condition that predominantly affects women. This study aimed to test the hypothesis that stress increases the risk of developing TMJ pain by facilitating inflammatory mechanisms in female and male rats.

Anti-hyperalgesic effects of photobiomodulation therapy (904 nm) on streptozotocin-induced diabetic neuropathy imply MAPK pathway and calcium dynamics modulation.

Several recent studies have established the efficacy of photobiomodulation therapy (PBMT) in painful clinical conditions. Diabetic neuropathy (DN) can be related to activating mitogen-activated protein kinases (MAPK), such as p38, in the peripheral nerve. MAPK pathway is activated in response to extracellular stimuli, including interleukins TNF-α and IL-1β.

Neutrophil-Derived COX-2 has a Key Role during Inflammatory Hyperalgesia.

Inflammation is a vital process for the injured tissue restoration and one of its hallmarks is inflammatory hyperalgesia. The cyclooxygenase (COX) pathway is strongly related to the inflammatory and painful process. Usually, the COX-1 isoform is described as homeostatic, while COX-2 is characterized as inducible in inflammatory conditions.

P2X7-induced nociception in the temporomandibular joint of rats depends on inflammatory mechanisms and C-fibres sensitization.

Background: P2X7 receptors are responsible for triggering inflammatory responses contributing to processes of pain in articular tissues. This study aimed to investigate whether the activation of the P2X7 receptor located in the temporomandibular joint (TMJ) tissues induces nociception through an inflammatory mechanisms and/or the activation of C-fibres (small-diameter primary afferents) of rats' TMJ.

Methods: The TMJ hypernociception induced by the activation of P2X7 receptor was assessed by measuring the behavioural nociceptive responses.

Running wheel exercise induces therapeutic and preventive effects on inflammatory stimulus-induced persistent hyperalgesia in mice.

Chronic pain affects significant portion of the world's population and physical exercise has been extensively indicated as non-pharmacological clinical intervention to relieve symptoms in chronic pain conditions. In general, studies on pain chronification and physical exercise intervention have focused on neuropathic pain, although chronic pain commonly results from an original inflammatory episode. Based on this, the objective of the present study was to investigate the therapeutic and preventive effect of the running wheel exercise on the persistent hyperalgesia induced by repetitive inflammatory stimulus, a rodent model that simulates clinical conditions of chronic pain that persist even with no more inflammatory stimulus present.

Inflammatory pain in peripheral tissue depends on the activation of the TNF-α type 1 receptor in the primary afferent neuron.

The mechanism underlying the role of tumor necrosis factor alpha (TNF-α) in the development of inflammatory hyperalgesia has been extensively studied, mainly the role of TNF-α in the release of pro-inflammatory cytokines. The current concept relies in the fact that TNF-α stimulates the cascade release of other pro-inflammatory cytokines, such as IL-1β, IL-6, and IL-8 (CINC-1 in rats), triggering the release of the final inflammatory mediator prostaglandin E (PGE ) and sympathetic amines that directly sensitize the nociceptors. However, this may not be the sole mechanism involved as the blockade of TNF-α synthesis by thalidomide prevents hyperalgesia without interrupting the synthesis of IL-1β, IL-6, and CINC-1.

CB receptor-dependent desensitisation of TRPV1 channels contributes to the analgesic effect of dipyrone in sensitised primary sensory neurons.

Background And Purpose: While dipyrone is a widely used analgesic, its mechanism of action is not completely understood. Recently, we have reported that the dipyrone metabolite 4-aminoantipyrine (4-AA) reduces PGE -induced pain-related behaviour through cannabinoid CB receptors. Here, we ascertained, in naive and PGE -induced "inflamed" conditions, both in vivo and in vitro, the molecular mechanisms involved in the 4-AA-induced analgesic effects.

Peripheral Inflammatory Hyperalgesia Depends on P2X7 Receptors in Satellite Glial Cells.

Peripheral inflammatory hyperalgesia depends on the sensitization of primary nociceptive neurons. Inflammation drives molecular alterations not only locally but also in the dorsal root ganglion (DRG) where interleukin-1 beta (IL-1β) and purinoceptors are upregulated. Activation of the P2X7 purinoceptors by ATP is essential for IL-1β maturation and release.

The onset speed of hyperglycemia is important to the development of neuropathic hyperalgesia in streptozotocin-induced diabetic rats.

Diabetic neuropathic hyperalgesia is one of the most common diabetes complications. The physiopathological mechanism of hyperalgesia and the reason by which this condition affects only part of the diabetic patients still unclear. We tested whether an adaptation of primary afferent neurons to hyperglycemia could prevent the development of hyperalgesia.

P2X3 and P2X2/3 receptors activation induces articular hyperalgesia by an indirect sensitization of the primary afferent nociceptor in the rats' knee joint.

We have previously shown that endogenous adenosine 5'-triphosphate (ATP), via P2X3 and P2X2/3 receptors, plays an essential role in carrageenan-induced articular hyperalgesia model in rats' knee joint. In the present study, we used the rat knee joint incapacitation test, Enzyme-Linked Immunosorbent Assay (ELISA), and myeloperoxidase enzyme activity assay, to test the hypothesis that the activation of P2X3 and P2X2/3 receptors by their agonist induces articular hyperalgesia mediated by the inflammatory mediators bradykinin, prostaglandin, sympathomimetic amines, pro-inflammatory cytokines and by neutrophil migration. We also tested the hypothesis that the activation of P2X3 and P2X2/3 receptors contributes to the articular hyperalgesia induced by the inflammatory mediators belonging to carrageenan inflammatory cascade.

Dipyrone is locally hydrolyzed to 4-methylaminoantipyrine and its antihyperalgesic effect depends on CB and kappa-opioid receptors activation.

Dipyrone is an analgesic pro-drug used clinically to control moderate pain with a high analgesic efficacy and low toxicity. Dipyrone is hydrolyzed to 4-methylaminoantipyrine (4-MAA), which is metabolized to 4-aminoantipyrine (4-AA). Here, were investigate the involvement of peripheral cannabinoid CB and opioid receptor activation in the local antihyperalgesic effect of dipyrone and 4-MAA.

Leukocyte-rich PRP versus leukocyte-poor PRP The role of monocyte/macrophage function in the healing cascade.

The mechanism of action of Platelet Rich Plasma (PRP) is thought to be related to the biomolecules present in α-granules. However, for the healing process to occur, an inflammatory phase is also deemed necessary. Leukocytes present in the inflammatory phase release both pro- and anti-inflammatory molecules.

Diabetes-induced Neuropathic Mechanical Hyperalgesia Depends on P2X4 Receptor Activation in Dorsal Root Ganglia.

Peripheral diabetic neuropathy (PDN) manifests in 50-60% of type I and II diabetic patients and is the major cause of limb amputation. Adequate therapy for PDN is a current challenge. There are evidences that the activation of the P2X4 receptor (P2X4R) expressed on microglial cells of the central nervous system takes part in the development of neuropathic pain.

Pain chronification and chronic pain impair a defensive behavior, but not the ability of acute pain to facilitate it, through the activation of an endogenous analgesia circuit.

The endogenous ability to decrease pain perception during life-threatening situations is crucial to the prevention of recuperative behaviors and to leave the subject free to engage in appropriated defensive responses. We have previously shown that acute pain activates the ascending nociceptive control-an endogenous analgesia circuit dependent on opioid mechanisms within nucleus accumbens-to facilitate the tonic immobility response, an innate defensive behavior. Now we asked whether chronic pain and pain chronification impairs either the tonic immobility response or the ability of acute pain to facilitate it by activating the ascending nociceptive control.

Social defeat stress induces hyperalgesia and increases truncated BDNF isoforms in the nucleus accumbens regardless of the depressive-like behavior induction in mice.

Epidemiological studies have shown a close association between pain and depression. There is evidence showing this association as patients with depression show a high chronic pain prevalence and vice versa. Considering that social stress is critical for the development of depression in humans, we used a social defeat stress (SDS) model which induces depressive-like behavior in mice.

Transcriptome analysis of dorsal root ganglia's diabetic neuropathy reveals mechanisms involved in pain and regeneration.

Unlabelled: Peripheral diabetic neuropathy (DN) manifests in nearly 60% of diabetic patients, being pain its most debilitating symptom. Although electrophysiological and morphological aspects are well described, little is known about its development and progression, undermining effective therapies. Hyperglycemia and insulin signaling impairment are considered the triggering events of oxidative stress observed in the dying nerves, however there are still many gaps in the knowledge of intracellular plastic changes it generates.

Local administration of mangiferin prevents experimental inflammatory mechanical hyperalgesia through CINC-1/epinephrine/PKA pathway and TNF-α inhibition.

Steroidal and non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to control inflammatory pain, but there is a risk of gastrointestinal bleeding and increased heart failure risk. The search for new drugs remains ongoing, and natural products are a source for potential new compounds. Mangiferin, a natural xanthone C-glucoside, has demonstrated biological activity, including anti-inflammatory and analgesic properties, but it's mechanisms are poorly understood.