scholarly journals Long-Lasting, Antinociceptive Effects of pH-Sensitive Niosomes Loaded with Ibuprofen in Acute and Chronic Models of Pain

Pharmaceutics ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 62 ◽  
Author(s):  
Francesca Marzoli ◽  
Carlotta Marianecci ◽  
Federica Rinaldi ◽  
Daniele Passeri ◽  
Marco Rossi ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Inflammatory Pain ◽  
Ph Sensitive ◽  
Free Form ◽  
Writhing Test ◽  
Polysorbate 20 ◽  
Antinociceptive Effects ◽  
Effects Of Ph ◽  
Inflammatory Drugs ◽  
Chronic Models

Ibuprofen is one of the non-steroidal anti-inflammatory drugs (NSAIDs) widely used to treat pain conditions. NSAIDs encounter several obstacles to passing across biological membranes. To overcome these constraints, we decided to study the effects of a new pH-sensitive formulation of niosomes containing Polysorbate 20 derivatized by Glycine and loaded with ibuprofen (NioIbu) in several animal models of pain in mice. We performed two tests commonly used to study acute antinociceptive activity, namely the writhing test and the capsaicin test. Our results demonstrated that NioIbu, administered 2 h before testing, reduced nociception, whereas the free form of ibuprofen was ineffective. In a model of inflammatory pain, hyperalgesia induced by zymosan, NioIbu induced a long-lasting reduction in hyperalgesia in treated mice. In a model of neuropathic pain induced by sciatic nerve chronic constriction, NioIbu reduced both neuropathy-induced allodynia and hyperalgesia. The results obtained in our experiments suggest that pH-sensitive niosomes containing Polysorbate 20 derivatized by Glycine is an effective model for NSAIDs delivery, providing durable antinociceptive effects and reducing the incidence of side effects.

scholarly journals Analgesic Effects and Impairment in Locomotor Activity Induced by Cannabinoid/Opioid Combinations in Rat Models of Chronic Pain

2020 ◽  
Vol 10 (8) ◽  
pp. 523
Author(s):  
Mohammad Alsalem ◽  
Ahmad Altarifi ◽  
Mansour Haddad ◽  
Belal Azab ◽  
Heba Kalbouneh ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
Locomotor Activity ◽  
Open Field ◽  
Field Test ◽  
Inflammatory Pain ◽  
Open Field Test ◽  
Antinociceptive Effect ◽  
Synthetic Cannabinoids ◽  
Antinociceptive Effects

Both opioids and cannabinoids have well-known antinociceptive effects in different animal models of chronic pain. However, unwanted side effects limit their use. The aim of this study is to evaluate the antinociceptive effect of combining synthetic cannabinoids with subtherapeutic doses of opioids, and to evaluate the effects of these drugs/combinations on rat’s locomotor activity. Intra-plantar injection of Complete Freund’s Adjuvant (CFA) into the left hindpaw and intraperitoneal injection of streptozotocin (STZ) were used to induce inflammatory and diabetic neuropathic pain in adult male Sprague-Dawley rats, respectively. Von Frey filaments were used to assess the antinociceptive effects of opioids (morphine and tramadol) and the synthetic cannabinoids (HU210 and WIN55212) or their combinations on CFA and STZ-induced mechanical allodynia. Open field test was used to evaluate the effect of these drugs or their combinations on locomotion. HU210 and WIN55212 did not produce significant antinociceptive effect on inflammatory pain while only the maximal dose of HU210 (1 mg/kg) was effective in neuropathic pain. Only the maximal doses of morphine (3.2 mg/kg) and tramadol (10 mg/kg) had significant anti-allodynic effects in both models. Tramadol (1 mg/kg) enhanced the antinociceptive effects of WIN55212 but not HU210 in neuropathic pain with no effect on inflammatory pain. However, in open field test, the aforementioned combination did not change tramadol-induced depression of locomotion. Tramadol and WIN55212 combination produces antinociceptive effects in neuropathic but not inflammatory pain at low doses with no additional risk of locomotor impairment, which may be useful in clinical practice.

scholarly journals Synergistic interaction between diclofenac and pyrilamine on nociception, inflammation, and gastric damage in rats

2017 ◽  
Vol 95 (1) ◽  
pp. 51-58 ◽  
Author(s):  
Mario I. Ortiz
Keyword(s):  
Animal Models ◽  
Clinical Management ◽  
Inflammatory Pain ◽  
Formalin Test ◽  
Mechanisms Of Action ◽  
Gastric Damage ◽  
Antinociceptive Effects ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Anti Inflammation

Experiments using nonsteroidal anti-inflammatory drugs (NSAIDs) alone have produced limited antinociceptive effects in animal models. For this reason, the number of studies involving the administration of NSAIDs along with an adjuvant drug harboring different mechanisms of action has increased enormously. Here, combinations of diclofenac and pyrilamine were used to determine their influence on nociception (formalin test), inflammation (paw inflammation produced by carrageenan), and gastric damage in rodents. Diclofenac, pyrilamine, or combinations of diclofenac and pyrilamine produced antinociceptive and anti-inflammatory effects in the rat. The systemic administration of diclofenac alone and in combination with pyrilamine produced significant gastric damage. Effective dose (ED) values were determined for each individual drug, and isobolograms were prepared. The theoretical ED values for the antinociceptive (systemic, 35.4 mg/kg; local, 343.4 μg/paw) and the anti-inflammatory (37.9 mg/kg) effects differed significantly from the experimental ED values (systemic antinociception, 18.1 mg/kg; local antinociception, 183.3 μg/paw; anti-inflammation, 10.6 mg/kg). Therefore, it was concluded that the interactions between diclofenac and pyrilamine are synergistic. The data suggest that the diclofenac–pyrilamine combinations can interact at the systemic and local peripheral levels, thereby offering a therapeutic alternative for the clinical management of inflammatory pain.

scholarly journals Selected pathobiological features and principles of pharmacological pain management

2020 ◽  
Vol 48 (5) ◽  
pp. 030006052090365
Author(s):  
Razia Abdool Gafaar Khammissa ◽  
Raoul Ballyram ◽  
Jeanine Fourie ◽  
Michael Bouckaert ◽  
Johan Lemmer ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
Pain Management ◽  
Nerve Injury ◽  
Inflammatory Pain ◽  
Opioid Analgesics ◽  
Neural Signals ◽  
Chronic Neuropathic Pain ◽  
Spinal Cord Neurons ◽  
Inflammatory Drugs

Pain induced by inflammation and nerve injury arises from abnormal neural activity of primary afferent nociceptors in response to tissue damage, which causes long-term elevation of the sensitivity and responsiveness of spinal cord neurons. Inflammatory pain typically resolves following resolution of inflammation; however, nerve injury—either peripheral or central—may cause persistent neuropathic pain, which frequently manifests as hyperalgesia or allodynia. Neuralgias, malignant metastatic bone disease, and diabetic neuropathy are some of the conditions associated with severe, often unremitting chronic pain that is both physically and psychologically debilitating or disabling. Therefore, optimal pain management for patients with chronic neuropathic pain requires a multimodal approach that comprises pharmacological and psychological interventions. Non-opioid analgesics (e.g., paracetamol, aspirin, or other non-steroidal anti-inflammatory drugs) are first-line agents used in the treatment of mild-to-moderate acute pain, while opioids of increasing potency are indicated for the treatment of persistent, moderate-to-severe inflammatory pain. N-methyl D-aspartate receptor antagonists, antidepressants, anticonvulsants, or a combination of these should be considered for the treatment of chronic neuropathic pain. This review discusses the various neural signals that mediate acute and chronic pain, as well as the general principles of pain management.

scholarly journals Clinical, behavioral and antinociceptive effects of crotalphine in horses

2015 ◽  
Vol 46 (4) ◽  
pp. 694-699
Author(s):  
Erica Cristina Bueno do Prado Guirro ◽  
João Henrique Perotta ◽  
Márcio de Paula ◽  
Yara Cury ◽  
Carlos Augusto Araújo Valadão
Keyword(s):  
Inflammatory Pain ◽  
Antinociceptive Effect ◽  
Behavioral Changes ◽  
Behavioral Effects ◽  
Phase Iii ◽  
Intact Skin ◽  
Kappa Opioid ◽  
Antinociceptive Effects ◽  
Analgesic Peptide ◽  
Scapular Region

ABSTRACT: Crotalphine is a novel analgesic peptide that acts on kappa opioid and delta receptors, causing powerful analgesia in rats submitted to inflammatory, neuropathic or oncologic models of pain. This study evaluated clinical, behavioral and antinociceptive effects caused by crotalphine in horses, employing 18 Arabian horses and it was divided in three phases. In Phase I, "clinical and behavioral effects", crotalphine did not change the latency to urinate and defecate; did not modify the values of cardiac or respiratory rates, intestinal motility and rectal temperature; and did not cause significant ataxia, head, eye and lip ptosis. In Phase II, "antinociceptive effect on intact skin at scapular or ischial region", crotalphine did not cause significant analgesia. In Phase III, "antinociceptive effect on incised skin at scapular or ischial region", crotalphine promoted effective antinociceptive effects for six hours and inhibited hyperalgesia state for three days in the ischial region of horses submitted to incisional model of inflammatory pain, but crotalphine did not evoke relevant analgesic effect on the scapular region. Concluding, intravenous injection of a single dose of crotalphine (3.8ngkg-1) did not cause important clinical or behavioral changes and promotes antinociceptive effect on incised ischial region for seven days in horses. Moreover, crotalphine did not evoke relevant anti nociceptive effect on the scapular region or in intact skin of horses.

The antinociceptive effects of magnesium sulfate and MK-801 in visceral inflammatory pain model: The role of NO/cGMP/K+ATP pathway

2015 ◽  
Vol 53 (11) ◽  
pp. 1621-1627 ◽  
Author(s):  
Sonja Vuckovic ◽  
Dragana Srebro ◽  
Katarina Savic Vujovic ◽  
Milica Prostran
Keyword(s):  
Magnesium Sulfate ◽  
Inflammatory Pain ◽  
Pain Model ◽  
Mk 801 ◽  
Antinociceptive Effects

scholarly journals Antinociceptive Efficacy of the µ-Opioid/Nociceptin Peptide-Based Hybrid KGNOP1 in Inflammatory Pain without Rewarding Effects in Mice: An Experimental Assessment and Molecular Docking

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3267
Author(s):  
Maria Dumitrascuta ◽  
Marcel Bermudez ◽  
Olga Trovato ◽  
Jolien De Neve ◽  
Steven Ballet ◽  
...  
Keyword(s):  
Mouse Models ◽  
Inflammatory Pain ◽  
Formalin Test ◽  
Subcutaneous Administration ◽  
Thermal Hyperalgesia ◽  
Nop Receptor ◽  
3D Interaction ◽  
Duration Of Action ◽  
Health Crisis ◽  
Antinociceptive Effects

Opioids are the most effective analgesics, with most clinically available opioids being agonists to the µ-opioid receptor (MOR). The MOR is also responsible for their unwanted effects, including reward and opioid misuse leading to the current public health crisis. The imperative need for safer, non-addictive pain therapies drives the search for novel leads and new treatment strategies. In this study, the recently discovered MOR/nociceptin (NOP) receptor peptide hybrid KGNOP1 (H-Dmt-D-Arg-Aba-β-Ala-Arg-Tyr-Tyr-Arg-Ile-Lys-NH2) was evaluated following subcutaneous administration in mouse models of acute (formalin test) and chronic inflammatory pain (Complete Freund’s adjuvant-induced paw hyperalgesia), liabilities of spontaneous locomotion, conditioned place preference, and the withdrawal syndrome. KGNOP1 demonstrated dose-dependent antinociceptive effects in the formalin test, and efficacy in attenuating thermal hyperalgesia with prolonged duration of action. Antinociceptive effects of KGNOP1 were reversed by naltrexone and SB-612111, indicating the involvement of both MOR and NOP receptor agonism. In comparison with morphine, KGNOP1 was more potent and effective in mouse models of inflammatory pain. Unlike morphine, KGNOP1 displayed reduced detrimental liabilities, as no locomotor impairment nor rewarding and withdrawal effects were observed. Docking of KGNOP1 to the MOR and NOP receptors and subsequent 3D interaction pattern analyses provided valuable insights into its binding mode. The mixed MOR/NOP receptor peptide KGNOP1 holds promise in the effort to develop new analgesics for the treatment of various pain states with fewer MOR-mediated side effects, particularly abuse and dependence liabilities.

Additive Antinociceptive Effects of the Selective Nav1.8 Blocker A-803467 and Selective TRPV1 Antagonists in Rat Inflammatory and Neuropathic Pain Models

2009 ◽  
Vol 10 (3) ◽  
pp. 306-315 ◽  
Author(s):  
S.K. Joshi ◽  
Prisca Honore ◽  
Gricelda Hernandez ◽  
Robert Schmidt ◽  
Arthur Gomtsyan ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Pain Models ◽  
Antinociceptive Effects
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