Browse by Audience
Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most prevalent and difficult-to-treat symptoms in cancer patients. For this reason, the explore for unused helpful choices able of filling these impediments is essential. Natural products from plants stand out as a valuable source of therapeutic agents, being options for the treatment of this growing public health problem. Therefore, the objective of this study was to report the effects of natural products from plants and the mechanisms of action involved in the reduction of neuropathy caused by chemotherapy. The search was performed in PubMed, Scopus and Web of Science in March/2021. Two reviewers independently selected the articles and extracted data on characteristics, methods, study results and methodological quality (SYRCLE). Twenty-two studies were selected, describing the potential effect of 22 different phytochemicals in the treatment of CIPN, with emphasis on terpenes, flavonoids and alkaloids. The effect of these compounds was demonstrated in different experimental protocols, with several action targets being proposed, such as modulation of inflammatory mediators and reduction of oxidative stress. The studies demonstrated a predominance of the risk of uncertain bias for randomization, baseline characteristics and concealment of the experimental groups. Our findings suggest a potential antinociceptive effect of natural products from plants on CIPN, probably acting in several places of action, being strategic for the development of new therapeutic options for this multifactorial condition.
Learn More >To explore the effect of moxibustion instrument combined with ultrashort wave on pain and oxidative stress in elderly patients with knee osteoarthritis (KOA).
Learn More >Votucalis is a biologically active protein in tick () saliva, which specifically binds histamine with high affinity and, therefore, has the potential to inhibit the host's immunological responses at the feeding site. We hypothesized that scavenging of peripherally released endogenous histamine by Votucalis results in both anti-itch and anti-nociceptive effects. To test this hypothesis, adult male mice were subjected to histaminergic itch, as well as peripheral nerve injury that resulted in neuropathic pain. Thus, we selected models where peripherally released histamine was shown to be a key regulator. In these models, the animals received systemic (intraperitoneal, i.p.) or peripheral transdermal (subcutaneous, s.c. or intraplantar, i.pl.) administrations of Votucalis and itch behavior, as well as mechanical and thermal hypersensitivity, were evaluated. Selective histamine receptor antagonists were used to determine the involvement of histamine receptors in the effects produced by Votucalis. We also used the spontaneous object recognition test to confirm the centrally sparing properties of Votucalis. Our main finding shows that in histamine-dependent itch and neuropathic pain models peripheral (s.c. or i.pl.) administration of Votucalis displayed a longer duration of action for a lower dose range, when compared with Votucalis systemic (i.p.) effects. Stronger anti-itch effect was observed after co-administration of Votucalis (s.c.) and antagonists that inhibited peripheral histamine H and H receptors as well as central histamine H receptors indicating the importance of these histamine receptors in itch. In neuropathic mice, Votucalis produced a potent and complete anti-nociceptive effect on mechanical hypersensitivity, while thermal (heat) hypersensitivity was largely unaffected. Overall, our findings further emphasize the key role for histamine in the regulation of histaminergic itch and chronic neuropathic pain. Given the effectiveness of Votucalis after peripheral transdermal administration, with a lack of central effects, we provide here the first evidence that scavenging of peripherally released histamine by Votucalis may represent a novel therapeutically effective and safe long-term strategy for the management of these refractory health conditions.
Learn More >Neuropathic pain is a refractory disease that occurs across the world and pharmacotherapy has limited efficacy and/or safety. This disease imposes a significant burden on both the somatic and mental health of patients; indeed, some patients have referred to neuropathic pain as being 'worse than death'. The pharmacological agents that are used to treat neuropathic pain at present can produce mild effects in certain patients, and induce many adverse reactions, such as sedation, dizziness, vomiting, and peripheral oedema. Therefore, there is an urgent need to discover novel drugs that are safer and more effective. Natural compounds from medical plants have become potential sources of analgesics, and evidence has shown that glycosides alleviated neuropathic pain via regulating oxidative stress, transcriptional regulation, ion channels, membrane receptors and so on. In this review, we summarize the epidemiology of neuropathic pain and the existing therapeutic drugs used for disease prevention and treatment. We also demonstrate how glycosides exhibit an antinociceptive effect on neuropathic pain in laboratory research and describe the antinociceptive mechanisms involved to facilitate the discovery of new drugs to improve the quality of life of patients experiencing neuropathic pain.
Learn More >C-shapes are stereotyped movements in planarians that are elicited by diverse stimuli (e.g. acidity, excitatory neurotransmitters, psychostimulants, and pro-convulsants). Muscle contraction and seizure contribute to the expression of C-shape movements, but a causative role for pain is understudied and unclear. Here, using nicotine-induced C-shapes as the endpoint, we tested the efficacy of three classes of antinociceptive compounds – an opioid, NSAID (non-steroidal anti-inflammatory drug), and transient receptor potential ankyrin 1 (TRPA1) channel antagonist. For comparison we also tested effects of a neuromuscular blocker. Nicotine (0.1-10 mM) concentration-dependently increased C-shapes. DAMGO (1-10 µM), a selective µ-opioid agonist, inhibited nicotine (5 mM)-induced C-shapes. Naloxone (0.1-10 µM), an opioid receptor antagonist, prevented the DAMGO (1 µM)-induced reduction of nicotine (5 mM)-evoked C-shapes, suggesting an opioid receptor mechanism. C-shapes induced by nicotine (5 mM) were also reduced by meloxicam (10-100 µM), a NSAID; HC 030031 (1-10 µM), a TRPA1 antagonist; and pancuronium (10-100 µM), a neuromuscular blocker. Evidence that nicotine-induced C-shapes are reduced by antinociceptive drugs from different classes, and require opioid receptor and TRPA1 channel activation, suggest C-shape etiology involves a pain component.
Learn More >Endometriosis is a difficult to manage condition associated with a significant disease burden. High levels of illicit cannabis use for therapeutic purposes have been previously reported by endometriosis patients in Australia and New Zealand (NZ). Although access to legal medicinal cannabis (MC) is available through medical prescription via multiple federal schemes, significant barriers to patient access remain. An anonymous cross-sectional online survey was developed and distributed through social media via endometriosis advocacy groups worldwide. Respondents were asked about legal versus illicit cannabis usage, their understanding of access pathways and legal status, and their interactions with health care professionals. Of 237 respondents who reported cannabis use with a medical diagnosis of endometriosis, 186 (72.0%) of Australian and 51 (88.2%) NZ respondents reported self-administering cannabis illicitly. Only 23.1% of Australian and 5.9% of NZ respondents accessed cannabis through a doctor's prescription, with 4.8% of Australian and no NZ respondents reporting to legally self-administer cannabis. Substantial substitution effects (>50% reduction) were observed in users of nonopioid analgesia (63.1%), opioid analgesia (66.1%), hormonal therapies (27.5%), antineuropathics (61.7%), antidepressants (28.2%) and antianxiety medications (47.9%). Of Australian respondents, 18.8% and of NZ respondents, 23.5% reported not disclosing their cannabis use to their medical doctor, citing concern over legal repercussions, societal judgment, or their doctors' reaction and presumed unwillingness to prescribe legal MC. Respondents self-reported positive outcomes when using cannabis for management of endometriosis, demonstrating a therapeutic potential for MC. Despite this, many are using cannabis without medical supervision. While evidence for a substantial substitution effect by cannabis was demonstrated in these data, of particular concern are the clinical consequences of using cannabis without medical supervision, particularly with regard to drug interactions and the tapering or cessation of certain medications without that supervision. Improving doctor and patient communication about MC use may improve levels of medical oversight, the preference for legal MC adoption over acquisition via illicit supply and reducing cannabis-associated stigma.
Learn More >Periodontitis progresses with chronic inflammation, without periodontal pain. However, the underlying mechanisms are not well known. Here, the involvement of butyric acid (BA) in periodontal pain sensitivity in Porphyromonas gingivalis (P. gingivalis)-induced periodontitis was examined.
Learn More >The aim of this study was to determine if prolactin signaling modulates stress-induced behavioral responses in a preclinical migraine model.
Learn More >The aim of this study is to evaluate the preemptive analgesic effects of dexamethasone (DEX) alone or combined with non-steroidal anti-inflammatory drugs (NSAIDs) in third molar surgeries. The subjects were divided into five groups (n = 20 teeth/group); subjects received only 8 mg of dexamethasone 1 h before the surgical procedure (DEX group), or in combination with etodolac (DEX + ETO), ketorolac (DEX + KET), ibuprofen (DEX + IBU), loxoprofen (DEX + LOX). Paracetamol 750 mg was provided as the number of rescue analgesics (NRA). Salivary PGE2 expression was measured preoperatively and at 48 h. Edema and Maximum mouth opening (MMO) were measured postoperatively at 48 h and 7 days. A visual analog scale (VAS) was performed postoperatively at 6, 12, 24, 48, 72 h, and 7 days. Salivary expression of PGE2 showed a decrease only for the DEX group. Edema and MMO and NRA consumption showed no significant differences among the groups (P > 0.05). The VAS showed a significantly lower pain perception at 6 h after the surgery for the DEX + ETO and DEX + KET groups (P < 0.05). The combination of DEX and NSAIDS should be considered for preemptive acute postsurgical pain management in third molar surgery. In some drug associations such as dexamethasone 8 mg + NSAIDS (ETO and KET) in the pre-operative time, only a few rescue analgesics are necessary.
Learn More >Activation of cannabinoid receptor type 1 (CB1) produces analgesia in a variety of preclinical models of pain; however, engagement of central CB1 receptors is accompanied by unwanted side effects, such as psychoactivity, tolerance and dependence. Therefore, some efforts to develop novel analgesics have focused on targeting peripheral CB1 receptors to circumvent central CB1-related side effects. In the present study, we evaluated the effects of acute and repeated dosing with the peripherally selective CB1-preferring agonist CB-13 on nociception and central CB1-related phenotypes in a model of inflammatory pain in mice. We also evaluated cellular mechanisms underlying CB-13-induced antinociception in vitro using cultured mouse dorsal root ganglion (DRG) neurons. CB-13 reduced inflammation-induced mechanical allodynia in male and female mice in a peripheral CB1 receptor-dependent manner and relieved inflammatory thermal hyperalgesia. In cultured mouse DRG neurons, CB-13 reduced TRPV1 sensitization and neuronal hyperexcitability induced by the inflammatory mediator prostaglandin E2, providing potential mechanistic explanations for the analgesic actions of peripheral CB1 receptor activation. With acute dosing, phenotypes associated with central CB1 receptor activation occurred only at a dose of CB-13 approximately 10-fold the ED50 for reducing allodynia. Strikingly, repeated dosing resulted in both analgesic tolerance and CB1 receptor dependence, even at a dose that did not produce central CB1 receptor-mediated phenotypes on acute dosing. This suggests repeated CB-13 dosing leads to increased CNS exposure and unwanted engagement of central CB1 receptors. Thus, caution is warranted regarding therapeutic use of CB-13 with the goal of avoiding CNS side effects. Nonetheless, the clear analgesic effect of acute peripheral CB1 receptor activation suggests that peripherally restricted cannabinoids are a viable target for novel analgesic development.
Learn More >