Biological evaluation and molecular docking studies of AA3052, a compound containing a μ-selective opioid peptide agonist DALDA and d-Phe-Phe-d-Phe-Leu-Leu-NH2, a substance P analogue.

The design of novel drugs for pain relief with improved analgesic properties and diminished side effect induction profile still remains a challenging pursuit. Tolerance is one of the most burdensome phenomena that may hamper ongoing opioid therapy, especially in chronic pain patients. Therefore, a promising strategy of hybridizing two pharmacophores that target distinct binding sites involved in pain modulation and transmission was established.

Morphine Analgesia Modification in Normotensive and Hypertensive Female Rats after Repeated Fluoxetine Administration.

The purpose of this investigation was to determine through the use of fluoxetine the effect of administering a serotonin reuptake inhibitor over several days on the antinociceptive action of μ-morphine type opioid receptor agonist. Investigations were performed on rats of both sexes, both the WKY normotensive strains as well as on the SHR genetically conditioned hypertensive strains. Results showed that the efficacy of morphine analgesia is higher in the SHR strain compared to normotensive rats (WKY).

Enhancement of antinociceptive effect of morphine by antidepressants in diabetic neuropathic pain model.

Background: Recent studies have shown that influence of antidepressants on analgesic action of opioids is heterogeneous. The aim of this study was to investigate the effect of acute and repeated (21 days) antidepressant (amitriptyline, moclobemide and reboxetine) treatment on the antinociceptive action of morphine, an opioid agonist, in streptozotocin (STZ)-induced neuropathic pain model.

Methods: The studies were performed on the male Wistar rats.

Dose-depending effect of intracerebroventricularly administered bradykinin on nociception in rats.

Background: The effect of small and high doses of intracerebroventricularly (icv) applied bradykinin (BK) on nociception produced by mechanical stimuli and the participation of B1 and B2 receptors in this nociception were investigated in rats.

Results: BK at the lowest dose (0.06 μg) produced hyperalgesia whereas at the higher doses (6 and 12 μg) antinociception.

Modification of morphine analgesia by venlafaxine in diabetic neuropathic pain model.

Background: The purpose of this study was to investigate the influence of single or chronic (21 days) administration of the serotonin and noradrenaline reuptake inhibitor, venlafaxine, on the antinociceptive action of the opioid receptor agonist, morphine, in streptozotocin (STZ)-induced hyperalgesia.

Methods: The studies were performed on male Wistar rats. Changes in nociceptive thresholds were determined using mechanical stimuli.

Venlafaxine and neuropathic pain.

The possible mechanisms involved in the antinociceptive effect of venlafaxine (VFX), a selective serotonin and noradrenaline reuptake inhibitor, after a single administration and chronic treatment were investigated in a diabetic neuropathic pain (DNP) model. VFX produced a significant antihyperalgesic effect after a single and repeated administration. This effect was reversed by pretreatment with yohimbine (a relatively selective α(2)-adrenergic antagonist) and p-chloroamphetamine (a neurotoxin which destroys serotonergic neurons).

Influence of acute and subchronic oral administration of dehydroepiandrosterone (DHEA) on nociceptive threshold in rats.

Background: Dehydroepiandrosterone (DHEA), a neurosteroid, is known to be the most abundant hormone in the human body. Its role in the central nervous system has not been well defined. Previous studies indicate that DHEA is synthesized in the spinal cord and plays an important role in pain modulation.

Magnesium ions and opioid agonists in vincristine-induced neuropathy.

Neuropathic pain is difficult to treat. Classic analgesics (i.e.

Modification of fentanyl analgesia by antidepressants.

Clinical practice often requires simultaneous administration of antidepressants with opioids (oncology, rheumatology). Coadministration may either attenuate or potentiate opioid analgesia. The purpose of this paper was to verify how the analgesic action of fentanyl (0.

Bradykinin receptor antagonists and cyclooxygenase inhibitors in vincristine- and streptozotocin-induced hyperalgesia.

Pain that accompanies neuropathy is difficult to treat. Analgesics administered as monotherapies possess low activities in relieving this kind of pain. The effect of the simultaneous administration of indomethacin (a preferential inhibitor of cyclooxygenase-1; COX-1) or celecoxib (a relatively selective inhibitor of cyclooxygenase-2; COX-2), with selective antagonists of bradykinin(2) (B(2)) bradykinin(1) (B(1)) receptors (HOE 140 or des-Arg(10)-HOE 140) on the alleviation of diabetic and toxic neuropathic pain was investigated.

Bradykinin receptors antagonists and nitric oxide synthase inhibitors in vincristine and streptozotocin induced hyperalgesia in chemotherapy and diabetic neuropathy rat model.

Purpose: The influence of an irreversible inhibitor of constitutive NO synthase (L-NOArg; 1.0 mg/kg ip), a relatively selective inhibitor of inducible NO synthase (L-NIL; 1.0 mg/kg ip) and a relatively specific inhibitor of neuronal NO synthase (7-NI; 0.

Sex dependent antinociceptive activity and blood pressure changes in SHR, WKY and WAG rat strains after diclofenac treatment.

Antinociceptive action of diclofenac (non-opioid analgesic) was investigated in male and female normotensive (WKY) and genetically established hypertensive (SHR) and normotensive WAG. The drug was administered subcutaneously in doses of 10 mg/kg body weight and per os 20 mg/kg and 40 mg/kg. Statistically significant differences in pain threshold were reported between male and female rats of investigated strains.

Alpha(1) and alpha(2)-adrenoreceptor antagonists in streptozotocin- and vincristine-induced hyperalgesia.

The effect of alpha(1)- and alpha(2)-adrenoreceptor antagonists (prazosin and yohimbine, respectively) on streptozotocin (STZ)- and vincristine (VIN)-induced hyperalgesia in rats was studied. In two experimental models, yohimbine (1.0 mg/kg ip) completely abolished STZ and VIN-induced hyperalgesia.

Magnesium ions and opioid agonist activity in streptozotocin-induced hyperalgesia.

Streptozotocin-induced hyperglycemia accompanied by a chronic decrease in the nociceptive threshold is considered a useful model of experimental hyperalgesia. We examined (1) the effect of the opioid receptor agonists and (2) the effect of the magnesium ions (Mg(2+)) on the antinociceptive action of opioid agonists in a diabetic neuropathic pain model. When administered alone, opioid agonists like morphine (5 mg/kg i.