tapentadol and Nociceptive-Pain

Chronic pain is a highly prevalent medical problem in the United States. Although opioids and serotonin-norepinephrine reuptake inhibitors (SNRIs) have demonstrated efficacy for relief of chronic pain, each has risks of adverse events in patients. Because of the risk of opioid abuse and addiction, combinations reducing opioid requirements are particularly valuable. Opioid and SNRI agents relieve pain by different pathways; concurrent use of each agent separately offers many potential benefits: complementary and possibly synergistic analgesic efficacy, separate titrations of opioid and SNRI effects, and the reduction of opioid requirements. However, few clinical studies have investigated the ideal ratios for combinations of opioids and SNRIs. A number of factors affect whether specific combinations have additive, synergistic, less than additive efficacy, or increase adverse events in patients, including general pharmacokinetic considerations, the potential for pharmacodynamic drug interactions, dose, and timing. Because there is little clinical evidence guiding combination therapy with separate opioid and SNRI agents, using single-molecule agents provides safe and effective therapy and should be the first option presented to patients. The use of empiric combinations of separate opioid and SNRI combinations needs to be considered in light of clinical cautions, including the lack of published evidence to guide dose conversion from any opioid to tramadol or to tapentadol, and vice versa; the need to avoid combinations with known drug interactions; and the need to titrate the dose when adding an SNRI to an opioid, and vice versa.

Topics: Analgesics, Opioid; Chronic Pain; Drug Combinations; Female; Humans; Middle Aged; Nociceptive Pain; Phenols; Selective Serotonin Reuptake Inhibitors; Tapentadol; Tramadol

Topics: Analgesics, Opioid; Humans; Neuralgia; Nociceptive Pain; Phenols; Tapentadol

To evaluate the onset, magnitude and duration of thermal antinociception after oral administration of two doses of tapentadol in cats.. Prospective, randomized, blinded, experimental study.. Six healthy adult cats weighing 4.4 ± 0.4 kg.. Skin temperature (ST) and thermal threshold (TT) were evaluated using a wireless TT device up to 12 hours after treatment. Treatments included placebo (PBO, 50 mg dextrose anhydrase orally), buprenorphine (BUP, 0.02 mg kg. Salivation was observed immediately following 11 out of 12 treatments with tapentadol. The ST was significantly increased at various time points in the opioid treatments. Hyperthermia (≥ 39.5 °C) was not observed. Baseline TT was 45.4 ± 1.4 °C for all treatments. Maximum TT values were 48.8 ± 4.8 °C at 1 hour in LowTAP, 48.5 ± 3.0 °C at 2 hours in HighTAP and 50.2 ± 5.3 °C at 1 hour in BUP. TT significantly increased after LowTAP at 1 hour, after HighTAP at 1-2 hours, and after BUP at 1-2 hours compared with baseline values. TTs were significantly increased in BUP at 1-2 hours compared with PBO.. Oral administration of tapentadol increased ST and TT in cats. The durations of thermal antinociception were similar between HighTAP and BUP, both of which were twice as long as that in LowTAP. Studies of different formulations may be necessary before tapentadol can be accepted into feline practice.

Topics: Administration, Oral; Analgesics, Opioid; Animals; Biological Availability; Buprenorphine; Cats; Cross-Over Studies; Female; Hot Temperature; Male; Nociceptive Pain; Pain Threshold; Phenols; Prospective Studies; Skin Temperature; Tapentadol

Dezocine and pentazocine, widely prescribed in China for postoperative pain, were initially considered as mixed agonist/antagonist targeting μ-opioid receptors (MORs) and κ-opioid receptors (KORs). However, dezocine has been revealed to alleviate chronic neuropathic pain through MOR activation and norepinephrine reuptake inhibition (NRI). This study investigated dezocine- and pentazocine-induced antinociception and physical dependence development, compared to the typical MOR-NRI opioid tapentadol.. Calcium mobilization assay was conducted to assess the potency of the drugs while hot-plate test was performed to compare the antinociception. Physical dependence development was compared with morphine.. Treatment with dezocine, pentazocine and tapentadol stimulated calcium mobilization in HEK293 cells stably expressed MORs but not KORs, whereas dezocine and pentazocine inhibited KOR activities. Subcutaneously injected dezocine-, tapentadol- and pentazocine-induced antinociception dose-dependently, in hot-plate test. Intrathecally injected MOR antagonist CTAP, norepinephrine depletor 6-OHDA and α. Our findings illustrated that dezocine and tapentadol, but not pentazocine, exert remarkable antinociception in nociceptive pain with less abuse liability via dual mechanisms of MOR activation and NRI.

Topics: Adrenergic Uptake Inhibitors; Analgesics, Opioid; Animals; Bridged Bicyclo Compounds, Heterocyclic; Drug Agonism; Drug Antagonism; HEK293 Cells; Humans; Mice; Nociceptive Pain; Pentazocine; Receptors, Adrenergic; Receptors, Opioid, kappa; Receptors, Opioid, mu; Tapentadol; Tetrahydronaphthalenes

The purpose of this study was to evaluate the antinociceptive interaction between dexketoprofen and tapentadol in three different dose ratios, as well as the ulcerogenic activity of this combination. Dose-response curves were carried out for dexketoprofen, tapentadol, and dexketoprofen-tapentadol combinations in the acetic acid-induced writhing test in mice. On the other hand, the gastric damage of all treatments was assessed after the surgical extraction of the stomachs. Intraperitoneal administration of dexketoprofen and tapentadol induced a dose-dependent antinociceptive effect, reaching a maximal effect of about 58% and 99%, respectively. Isobolographic analysis and the interaction index showed that the three proportions produced an analgesic potentiation (synergistic interaction). Interestingly, the 1:1 and 1:3 ratios of the drugs combination produced minor gastric injury in comparison with the 3:1 proportion. Our data suggest that all proportions of the dexketoprofen-tapentadol combination produced a synergistic interaction in the acetic acid-induced visceral pain model in mice with a low incidence of gastric injury.

Topics: Analgesics; Animals; Dose-Response Relationship, Drug; Drug Combinations; Drug Synergism; Ketoprofen; Male; Mice; Mice, Inbred BALB C; Nociceptive Pain; Pain Measurement; Stomach Ulcer; Tapentadol; Tromethamine