Clinical, behavioral and antinociceptive effects of crotalphine in horses

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.

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Morphine Antinociception Restored by Use of Methadone in the Morphine-Resistant Inflammatory Pain State

Frontiers in Pharmacology ◽

10.3389/fphar.2020.593647 ◽

2020 ◽

Vol 11 ◽

Author(s):

Chizuko Watanabe ◽

Asami Komiyama ◽

Masaru Yoshizumi ◽

Shinobu Sakurada ◽

Hirokazu Mizoguchi

Keyword(s):

Opioid Receptors ◽

Inflammatory Pain ◽

Antinociceptive Effect ◽

Thermal Hyperalgesia ◽

Expression Level ◽

Pain Model ◽

Mk 801 ◽

Antinociceptive Effects ◽

Pain State ◽

Intraperitoneal Treatment

The antinociceptive effect of methadone in the morphine-resistant inflammatory pain state was described in the paw-withdrawal test using the complete Freund’s adjuvant (CFA)-induced mouse inflammatory pain model. After intraplantar (i.pl.) injection of CFA, thermal hyperalgesia was observed in the ipsilateral paw. The antinociceptive effects of subcutaneous (s.c.) injection of morphine, fentanyl, and oxycodone against thermal hyperalgesia in the inflammatory pain state were reduced in the ipsilateral paw 7 days after CFA pretreatment. On the contrary, the antinociceptive effect of s.c. injection of methadone was maintained in the ipsilateral paw 7 days after CFA pretreatment. The suppressed morphine antinociception in the CFA model mice was bilaterally restored following s.c. treatment with methadone 20 min prior to or 3 days after CFA pretreatment. The suppressed morphine antinociception was also bilaterally restored by intraperitoneal treatment with MK-801 30 min prior to CFA pretreatment; however, the s.c. injection of morphine 30 min prior to CFA pretreatment failed to restore the suppressed morphine antinociception in the CFA model mice. The expression level of mRNA for µ-opioid receptors 7 days after i.pl. pretreatment was not significantly changed by i.pl. pretreatment with CFA or s.c. pretreatment with methadone. In conclusion, methadone is extremely effective against thermal hyperalgesia in the morphine-resistant inflammatory pain state, and restores suppressed morphine antinociception in the inflammatory pain state without altering the expression level of mRNA for µ-opioid receptors.

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NEONATAL PAIN MODULATES IN ADOLESCENT RATS THE ANTINOCICEPTIVE EFFECTS OF FLUOXETINE AND BUSPIRONE ADMINISTRATED TO THEIR DEPRESSIVE DAMS DURING GESTATION

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2020-0307 ◽

2020 ◽

Author(s):

Irina P Butkevich ◽

Viktor A Mikhailenko ◽

Elena A Vershinina

Keyword(s):

Inflammatory Pain ◽

Time Course ◽

Antinociceptive Effect ◽

Later Life ◽

Pain Response ◽

Neonatal Pain ◽

Antinociceptive Effects ◽

Prenatally Stressed ◽

Adolescent Rats ◽

Depressed Mothers

Abstract: Previously, we have shown that the administration of a selective serotonin reuptake inhibitor fluoxetine or a 5-HT1A receptor agonist buspirone to stressed rats during gestation causes in the offspring alleviation of formalin-induced pain, strengthened by prenatal stress. We have also found that neonatal inflammatory pain strengthens formalin-induced pain in prenatally unstressed rats in later life. In the present study we investigated the effect of neonatal inflammatory pain on the time-course of the biphasic pain response in the formalin test in prenatally stressed adolescent rats of both sexes to evaluate whether neonatal pain affects the antinociceptive properties of these drugs administered to their depressed mothers during gestation. Our findings demonstrate that neonatal pain modulates in prenatally stressed rats the antinociceptive effect of fluoxetine and buspirone depending on the level of organization of pain response in the CNS, the phase of the time-course of the formalin-induced pain, and sex.

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

Brain Sciences ◽

10.3390/brainsci10080523 ◽

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.

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Synergistic Antinociceptive Effect of Amitriptyline and Morphine in the Rat Orofacial Formalin Test

Anesthesiology ◽

10.1097/00000542-200403000-00033 ◽

2004 ◽

Vol 100 (3) ◽

pp. 690-696 ◽

Cited By ~ 21

Author(s):

Philippe Luccarini ◽

Laurent Perrier ◽

Céline Dégoulange ◽

Anne-Marie Gaydier ◽

Radhouane Dallel

Keyword(s):

Confidence Interval ◽

Inflammatory Pain ◽

Formalin Test ◽

Antinociceptive Effect ◽

Second Phase ◽

Isobolographic Analysis ◽

Antinociceptive Effects ◽

Analgesic Agents ◽

Rubbing Behavior ◽

Orofacial Formalin Test

Background Combination therapy is often used to increase the clinical utility of analgesic agents. The coadministration of two compounds may achieve analgesia at doses lower than those required for either compound alone, leading to enhanced pain relief and reduction of adverse effects. Herein, the authors describe the effect of coadministration of morphine and amitriptyline on cutaneous orofacial inflammatory pain in rats. Methods Amitriptyline, morphine, or the combination of amitriptyline and morphine was administered systemically to rats, and antinociceptive effects were determined by means of the rat orofacial formalin test. Isobolographic analysis was used to define the nature of the interactions between morphine and amitriptyline. Results Amitriptyline as well as morphine produced a dose-related inhibition in the first phase and the second phase of rubbing activity. ED50 values against rubbing behavior were 14.6 mg/kg (95% confidence interval, 10.2-33.5 mg/kg) and 1.3 mg/kg (95% confidence interval, 1.0-1.7 mg/kg) for amitriptyline and morphine, respectively. Combinations of increasing fractional increments of amitriptyline and morphine ED50 doses produced a synergistic effect against rubbing behavior, as revealed by isobolographic analysis. Conclusions The current study suggests that systemic amitriptyline and morphine synergistically inhibit cutaneous orofacial inflammatory pain in rats.

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Antinociceptive Effects of Heterotopic Electroacupuncture in Formalin-Induced Pain

The American Journal of Chinese Medicine ◽

10.1142/s0192415x06004107 ◽

2006 ◽

Vol 34 (04) ◽

pp. 565-574 ◽

Cited By ~ 10

Author(s):

Jae Hyo Kim ◽

Young Seob Gwak ◽

Inhyung Lee ◽

In Churl Sohn ◽

Min Sun Kim ◽

...

Keyword(s):

Inflammatory Pain ◽

Spinal Dorsal Horn ◽

Late Phase ◽

Antinociceptive Effect ◽

Formalin Injection ◽

Spinal Dorsal ◽

Antinociceptive Effects ◽

C Fiber ◽

The Right ◽

Lumbar Spinal

This study examined the antinociceptive effect of electroacupuncture (EA) to heterotopic acupoints on formalin-induced pain in rats. EA (2 ms, 10 Hz, and 3 mA) was delivered to heterotopic acupoints HE7 and PE7, or non-acupoints at the right fore limb, for 30 min and was immediately followed by subcutaneous formalin injection into the left hind paw, respectively. The quantified pain score, electromyogram (EMG) response of the C-fiber reflex, and cFos immunoreactivity were assessed, respectively. EA to heterotopic acupoints significantly reduced both early- and late-phase pain-like behaviors and significantly decreased the EMG responses of the C-fiber reflex after formalin injection. By contrast, EA to non-acupoints had no significant effects on pain-like behavior or the EMG response. In addition, EA to heterotopic acupoints decreased cFos immunoreactivity in the lumbar spinal dorsal horn. Therefore, EA induced pre-emptive antinociception via the extra-segmental inhibition of the formalin-induced pain, suggesting that EA to heterotopic acupoints is a useful treatment for inflammatory pain.

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Involvement of Opioid System and TRPM8/TRPA1 Channels in the Antinociceptive Effect of Spirulina platensis

Biomolecules ◽

10.3390/biom11040592 ◽

2021 ◽

Vol 11 (4) ◽

pp. 592

Author(s):

Mariana A. Freitas ◽

Amanda Vasconcelos ◽

Elaine C. D. Gonçalves ◽

Eduarda G. Ferrarini ◽

Gabriela B. Vieira ◽

...

Keyword(s):

Acetic Acid ◽

Spirulina Platensis ◽

Inflammatory Pain ◽

Motor Coordination ◽

Therapeutic Potential ◽

Antinociceptive Effect ◽

Significant Inhibition ◽

Inflammatory Phase ◽

Rodent Behavior ◽

Antinociceptive Effects

Spirulina platensis is a “super-food” and has attracted researchers’ attention due to its anti-inflammatory, antioxidant, and analgesic properties. Herein, we investigated the antinociceptive effects of Spirulina in different rodent behavior models of inflammatory pain. Male Swiss mice were treated with Spirulina (3–300 mg/kg, p.o.), indomethacin (10 mg/kg, p.o.), or vehicle (0.9% NaCl 10 mL/kg). Behavioral tests were performed with administration of acetic acid (0.6%, i.p.), formalin 2.7% (formaldehyde 1%, i.pl.), menthol (1.2 µmol/paw, i.pl.), cinnamaldehyde (10 nmol/paw, i.pl.), capsaicin (1.6 µg/paw, i.pl.), glutamate (20 µmol/paw, i.pl.), or naloxone (1 mg/kg, i.p.). The animals were also exposed to the rotarod and open field test to determine possible effects of Spirulina on locomotion and motor coordination. The quantitative phytochemical assays exhibited that Spirulina contains significant concentrations of total phenols and flavonoid contents, as well as it showed a powerful antioxidant effect with the highest scavenging activity. Oral administration of Spirulina completely inhibited the abdominal contortions induced by acetic acid (ED50 = 20.51 mg/kg). Spirulina treatment showed significant inhibition of formalin-induced nociceptive behavior during the inflammatory phase, and the opioid-selective antagonist markedly blocked this effect. Furthermore, our data indicate that the mechanisms underlying Spirulina analgesia appear to be related to its ability to modulate TRMP8 and TRPA1, but not by TRPV1 or glutamatergic system. Spirulina represents an orally active and safe natural analgesic that exhibits great therapeutic potential for managing inflammatory pain disorders.

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Comparison of Antinociceptive Effects Induced by Kappa Opioid Agonists in Male and Female Mice

Analgesia ◽

10.3727/107156999819565766 ◽

1999 ◽

Vol 4 (3) ◽

pp. 397-404 ◽

Cited By ~ 10

Author(s):

Corinne A. Patrick ◽

M. C. Holden Ko ◽

James H. Woods

Keyword(s):

Kappa Opioid ◽

Male And Female ◽

Female Mice ◽

Opioid Agonists ◽

Antinociceptive Effects

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Aristolochia trilobata: Identification of the Anti-Inflammatory and Antinociceptive Effects

Biomedicines ◽

10.3390/biomedicines8050111 ◽

2020 ◽

Vol 8 (5) ◽

pp. 111

Author(s):

Dayana da Costa Salomé ◽

Natália de Morais Cordeiro ◽

Tayná Sequeira Valério ◽

Darlisson de Alexandria Santos ◽

Péricles Barreto Alves ◽

...

Keyword(s):

Enzyme Inhibitor ◽

Interleukin 1 ◽

Antinociceptive Effect ◽

Cholinergic Receptor ◽

Hot Plate ◽

Nitric Oxide Synthase Inhibitor ◽

Antinociceptive Effects ◽

Anti Inflammatory ◽

Skin Affection ◽

Synthase Inhibitor

Aristolochia trilobata, popularly known as “mil-homens,” is widely used for treatment of stomach aches, colic, asthma, pulmonary diseases, diabetes, and skin affection. We evaluated the antinociceptive and anti-inflammatory activities of the essential oil (EO) and the main constituent, 6-methyl-5-hepten-2-yl acetate (sulcatyl acetate, SA). EO and SA (1, 10, and 100 mg/kg, p.o.) were evaluated using chemical (formalin-induced licking) and thermal (hot-plate) models of nociception or inflammation (carrageenan-induced cell migration into the subcutaneous air pouch, SAP). The mechanism of antinociceptive activity was evaluated using opioid, cholinergic receptor antagonists (naloxone and atropine), or nitric oxide synthase inhibitor (L-NAME). EO and SA presented a central antinociceptive effect (the hot-plate model). In formalin-induced licking response, higher doses of EO and SA also reduced 1st and 2nd phases. None of the antagonists and enzyme inhibitor reversed antinociceptive effects. EO and SA reduced the leukocyte migration into the SAP, and the cytokines tumor necrosis factor and interleukin-1 (TNF-α and IL-1β, respectively) produced in the exudate. Our results are indicative that EO and SA present peripheral and central antinociceptive and anti-inflammatory effects.

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