mobic and Neuralgia

To assess the safety of duloxetine at a fixed-dose of 60 mg twice daily (BID) for up to 52 weeks, and compare duloxetine with routine care in the management of patients with diabetic peripheral neuropathic pain (DPNP).. Patients who completed a 13-week, randomized, double-blind, placebo-controlled acute therapy period were randomly reassigned in a 2:1 ratio to therapy with duloxetine 60 mg BID (N = 197) or routine care (N = 96) for an additional 52 weeks.. The trial included outpatients > or =18 years of age diagnosed with moderate to severe DPNP caused by type 1 or type 2 diabetes.. Fourteen patients discontinued due to adverse events or death (11 [5.6%] duloxetine- and 3 [3.1%] routine care-treated patients). There were no significant therapy-group differences observed for patients with >/=1 serious adverse event. In total, 110 (55.8%) duloxetine- and 47 (49%) routine care-treated patients had > or =1 treatment-emergent adverse event (TEAE). The TEAE with a significant therapy-group difference, with patients in the duloxetine therapy group experiencing a higher percentage of events, was asthenia (11 [5.6%] duloxetine- vs no routine care-treated patients). Duloxetine did not appear to adversely affect lipid profiles, or nerve or eye function. There were no significant therapy-group differences observed in mean change in systolic blood pressure, weight, or electrocardiogram parameters. Significant therapy-group differences were observed in favor of duloxetine in the SF-36 physical component summary score, and subscale scores of physical functioning, bodily pain, mental health, and vitality.. The results of this study provide support for the use of duloxetine in the long-term management of DPNP.

Topics: Acetaminophen; Amitriptyline; Analgesics; Carbamazepine; Diabetes Complications; Diabetic Neuropathies; Diclofenac; Double-Blind Method; Duloxetine Hydrochloride; Female; Humans; Lipids; Male; Meloxicam; Middle Aged; Neuralgia; Pentoxifylline; Selective Serotonin Reuptake Inhibitors; Thiamine; Thiazines; Thiazoles; Thioctic Acid; Thiophenes; Time; Vitamin B 12

Canine neuropathic pain (NeuP) has been poorly investigated. This study aimed to evaluate the pain burden, sensory profile and inflammatory cytokines in dogs with naturally-occurring NeuP. Twenty-nine client-owned dogs with NeuP were included in a prospective, partially masked, randomized crossover clinical trial, and treated with gabapentin/placebo/gabapentin-meloxicam or gabapentin-meloxicam/placebo/gabapentin (each treatment block of 7 days; total 21 days). Pain scores, mechanical (MNT) and electrical (ENT) nociceptive thresholds and descending noxious inhibitory controls (DNIC) were assessed at baseline, days 7, 14, and 21. DNIC was evaluated using ΔMNT (after-before conditioning stimulus). Positive or negative ΔMNT corresponded to inhibitory or facilitatory pain profiles, respectively. Pain scores were recorded using the Client Specific Outcome Measures (CSOM), Canine Brief Pain Inventory (CBPI), and short-form Glasgow Composite Measure Pain Scale (CMPS-SF). Data from baseline were compared to those of sixteen healthy controls. ΔMNT, but not MNT and ENT, was significantly larger in controls (2.3 ± 0.9 N) than in NeuP (-0.2 ± 0.7 N). The percentage of dogs with facilitatory sensory profile was similar at baseline and after placebo (61.5-63%), and between controls and after gabapentin (33.3-34.6%). The CBPI scores were significantly different between gabapentin (CBPI pain and CBPI overall impression) and/or gabapentin-meloxicam (CBPI pain and interference) when compared with baseline, but not placebo. The CBPI scores were not significantly different between placebo and baseline. The concentration of cytokines was not different between groups or treatments. Dogs with NeuP have deficient inhibitory pain mechanisms. Pain burden was reduced after gabapentin and/or gabapentin-meloxicam when compared with baseline using CBPI and CMPS-SF scores. However, these scores were not superior than placebo, nor placebo was superior to baseline evaluations. A caregiver placebo effect may have biased the results.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Cytokines; Dog Diseases; Dogs; Female; Gabapentin; Inflammation; Inflammation Mediators; Male; Meloxicam; Neuralgia; Pain Measurement; Prospective Studies

Topics: Analgesics, Non-Narcotic; Female; Home Care Services; Humans; Injections, Spinal; Intervertebral Disc Displacement; Lumbosacral Plexus; Meloxicam; Middle Aged; Nerve Block; Neuralgia; Peripheral Nervous System Diseases

Although current neuropathic pain treatment guidelines do not recommend the use of nonsteroidal anti-inflammatory drugs (NSAIDs), whether NSAIDs can serve as a useful adjuvant to conventional multimodal therapy remains unclear.. The spared nerve injury (SNI) rats rapidly developed profound and long-lasting spontaneous and evoked pain behaviors, including mechanical and cold allodynia of the ipsilateral hind paw. At day 5, we first characterized the nociceptive responses to ketorolac, tramadol, pregabalin, and their combinations.. We found that tramadol and pregabalin exerted dose-dependent analgesic effects on both spontaneous and evoked behaviors. However, ketorolac alone did not suppress any behaviors regardless of the dose. Ketorolac-tramadol and ketorolac-pregabalin produced variable degrees of additive suppression of spontaneous and evoked behavioral responses. Cold allodynia was profoundly diminished after ketorolac was added to ineffective pregabalin or tramadol. Mechanical allodynia was markedly attenuated by ketorolac-pregabalin but less so by ketorolac-tramadol mixtures.. Our data demonstrated that an NSAID alone failed to relieve spontaneous or evoked pain behaviors in the rat SNI model, but when combined with a weak opioid and α-2-δ-ligand produced a profound synergistic analgesic effect on cold allodynia and discrepant efficacy for mechanical allodynia and spontaneous pain.

Topics: Animals; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Ketorolac; Male; Meloxicam; Neuralgia; Pregabalin; Rats; Rats, Sprague-Dawley; Tramadol

Although neck and low-back pain are common sources of neuropathic pain with high societal costs, the pathophysiology of neuropathic pain is not well-defined. Traditionally, most rodent pain studies rely on evoked reflex-based testing to measure pain. However, these testing methods do not reveal spontaneous pain, particularly early after injury. The rat grimace scale (RGS) for quantifying spontaneous pain has been validated after visceral, incisional, orthopedic, and inflammatory insults but not neuropathic pain. The current study used a rat model of radiculopathy to investigate the time course of RGS, the effect of the NSAID meloxicam on RGS, and the reliability and consistency of RGS across testers. RGS values at baseline and at 3, 6, 24, and 48 h after cervical nerve root compression (NRC) that induced robust evoked pain responses were compared with those obtained after sham surgery. The RGS was also evaluated at 6 h after NRC in another set of rats that had received meloxicam treatment prior to surgery. At 6 h, NRC induced higher RGS scores (1.27 ± 0.18) than did sham surgery (0.93 ± 0.20), and scores remained above baseline for as long as 48 h. Treatment with meloxicam before NRC reduced RGS at 6 h to sham levels, which were lower than those of injury without treatment. The RGS was associated with very good interobserver reliability (intraclass correlation coefficient, 0.91) and excellent internal consistency (Cronbach α, 0.87). These findings suggest that RGS is a useful approach to identifying and monitoring acute neuropathic pain in rats.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Disease Models, Animal; Facial Expression; Male; Meloxicam; Neuralgia; Pain Measurement; Radiculopathy; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Thiazines; Thiazoles; Time Factors; Video Recording

Preclinical Research Neuropathic pain is particularly difficult to treat because of its diverse etiologies and underlying pathophysiological mechanisms. Drug combinations have been proposed to effectively treat some neuropathies. In the present study the interaction of five combinations of meloxicam and gabapentin, were studied to assess the possible synergistic antinociceptive response in neuropathic pain using the von Frey and acetone tests in rat models. Coadministration of meloxicam and gabapentin increased the antihyperalgesic or antiallodynic effects as compared with the compounds administered alone. The area under the curve (AUC) of the antihyperalgesic effects produced by the combination of the two drugs was generally similar to the theoretical sum of effects produced by each drug alone. However, the AUC of the antiallodynic effect produced by one combination (meloxicam 1.0 mg/kg + gabapentin 10 mg/kg) was greater than the theoretical sum of the effects produced by each drug alone. The type of final interaction on the drug combinations can be additive or cause potentiation of antinociceptive effects and depends on the proportion of each compound used in dosing. Drug Dev Res 77 : 134-142, 2016. © 2016 Wiley Periodicals, Inc.

Topics: Amines; Analgesics; Animals; Area Under Curve; Cyclohexanecarboxylic Acids; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Gabapentin; gamma-Aminobutyric Acid; Male; Meloxicam; Neuralgia; Rats; Thiazines; Thiazoles; Treatment Outcome

Some antidepressants are effective for treating neuropathic pain independent of any effect on depression. Selective serotonin reuptake inhibitors (SSRIs) are one of the potential agents to treat neuropathic pain. The aims of this study were to compare the effects of SSRI and non-steroidal anti-inflammatory drugs (NSAIDs) on pain-related behavior and expression of cytokines in a rat model of neuropathic pain.. Spinal surgery was performed to apply nucleus pulposus (NP) to the dorsal root ganglion (DRG). NP animals were treated with saline (NP + S), meloxicam (NP + M), or low-dose or high-dose paroxetine (NP + PL and NP + PH), respectively. Behavioral testing was performed to investigate the mechanical withdrawal thresholds. The numbers of TNF-immunoreactive (IR) neurons in the DRG and of Iba1-IR microglia in the spinal cord (SC) were evaluated using immunohistochemistry. Expression of TNF in the DRG was examined using Western blots.. The thresholds on days 14, 21, and 28 were higher in the drug-treated animals than in the NP + S group (p < 0.05). The number of TNF-IR neurons in DRGs from the NP + M group increased on day 2 and decreased on day 7, and TNF expression in DRGs was significantly higher in the NP + S group than in the NP + M group on days 7, 14. The number of Iba1-IR microglia in the SC was significantly higher in the NP + S group than in the NP + M, NP + PL, and NP + PH groups on days 7 and 14.. An antidepressant might be a potential agent to treat lumbar disc herniation as well as NSAIDs.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Calcium-Binding Proteins; Disease Models, Animal; Ganglia, Spinal; Immunohistochemistry; Meloxicam; Microfilament Proteins; Microglia; Neuralgia; Neurons; Paroxetine; Rats; Rats, Sprague-Dawley; Selective Serotonin Reuptake Inhibitors; Thiazines; Thiazoles; Tumor Necrosis Factor-alpha

The objective of this study was to examine the effects of rofecoxib, meloxicam, both cyclooxygenase-2 (COX-2) inhibitors and aminoguanidine hydrochloride, an inducible nitric oxide synthase (iNOS) inhibitor and their combinations in neuropathic pain in rats.. Neuropathy was induced by chronic constriction injury (CCI) of right sciatic nerve under ketamine anesthesia in rats. Effect of ED(50) of aminoguanidine hydrochloride, rofecoxib and meloxicam administered orally was investigated using behavioral tests. Effect of combinations of aminoguanidine hydrochloride with rofecoxib and meloxicam was also investigated in neuropathic pain employing behavioral tests.. Behavioral tests, mechanical, thermal and cold stimuli confirmed the development of neuropathic pain after CCI. Aminoguanidine hydrochloride, rofecoxib and meloxicam when administered alone, produced significant increase in paw withdrawal threshold to mechanical stimuli at 6 h in ipsilateral hind paw after CCI. Co-administration of aminoguanidine hydrochloride (30 mg/kg) with rofecoxib (1.31 mg/kg) and meloxicam (1.34 mg/kg) was also found to produce significant increase in paw withdrawal latencies to mechanical stimuli at 6 h. Combined administration of aminoguanidine hydrochloride with meloxicam and rofecoxib produced significant rise in pain threshold for mechanical hyperalgesia in ipsilateral hind paw when compared with the groups treated with aminoguanidine hydrochloride, meloxicam and rofecoxib alone.. Co-administration of meloxicam and rofecoxib with aminoguanidine hydrochloride may be an alternative approach for the treatment of neuropathic pain.

Topics: Animals; Cyclooxygenase 2 Inhibitors; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Combinations; Drug Synergism; Guanidines; Hyperalgesia; Lactones; Male; Meloxicam; Neuralgia; Neurons, Afferent; Nitric Oxide; Nitric Oxide Synthase Type II; Nociceptors; Pain Threshold; Peripheral Nervous System Diseases; Physical Stimulation; Rats; Reaction Time; Sciatic Neuropathy; Sulfones; Thiazines; Thiazoles; Treatment Outcome