Retrospective Study of 240 Dogs Receiving Gabapentin for Chronic Pain Relief (original) (raw)
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The adverse effect profile of gabapentin in dogs
2018
Gabapentin, originally designed as an antiepileptic drug, has shown promising properties for treatment of neuropathic and chronic pain conditions in humans with diseases such as post herpetic neuralgia, amyotrophic lateral sclerosis (ALS) and diabetic neuropathy, but the evidence regarding analgesic effect, adverse reactions and dosing in animals remains sparse. Recommendations in human medicine are to progressively increase, and taper, dosing of gabapentin to minimize the risk of adverse effects. The most common adverse effects in humans are dizziness, somnolence, peripheral edema and gait disturbance. No studies have been conducted on adverse effects of gabapentin in dogs. The pharmacokinetics of gabapentin, in both humans and dogs, also suggest dosing three times daily to maintain concentrations considered therapeutical in humans. A retrospective study of dogs medicated with gabapentin at the University Animal Hospital in Uppsala was conducted between 1st of September 2017 and 1st of January 2018. The aim of this study was to evaluate the adverse effect profile of gabapentin in dogs. The main research hypothesis tested was if there is a dose relationship regarding the adverse effects seen in dogs, similar to that seen in humans. An additional hypothesis was if there are risk factors, such as not gradually increasing dosing, or peak serum concentrations, for developing adverse effects from gabapentin treatment. The study was conducted through a questionnaire sent out to owners of dogs medicated with gabapentin within the past two years. The first page of the questionnaire included several questions with a combination of open-and closed questions. The second part listed adverse effects that the owner graded using a 5-grade scale from "not present", "mild", "moderate", "severe" to "very severe". The questionnaire was conducted in Swedish and was sent out by mail. A total of 50% reported some type of adverse effect during treatment with gabapentin, but 12 of 16 dogs were, during the whole treatment, on multimodal treatment protocols. Neurological adverse effects, similar to those seen in humans on gabapentin treatment, were reported in five dogs. These adverse effects could not be related to other medications or disease symptoms. Four dogs underwent a period of monotherapy with gabapentin. No adverse effects were reported in these dogs. Despite recommendations in human medicine to gradually increase the gabapentin dose, only 4 of 16 dogs were prescribed a dosing regimen following these recommendations. A total of 6 dogs were administered gabapentin twice daily, whereas the remaining 10 received gabapentin 3 times daily. The study provided insight into dosing and effect of gabapentin in dogs. However, due to a small sample size and a relatively homogenous study group regarding dose range, and a large number of dogs on multimodal pain treatment, the study resulted in few conclusive findings regarding adverse effects of gabapentin in dogs. Insufficient knowledge about gabapentin's properties in dogs and other pets poses a risk that a drug that could potentially treat chronic pain conditions may be administered in a way that gives results in suboptimal, or not effective, blood concentrations. Therefore, more research is needed to determine the pharmacodynamics of gabapentin in dogs. For example, it is of paramount importance to further investigate if gabapentin provides the same analgesic effect for dogs as seen in studies of humans, as gabapentin may open possibilities of treating otherwise untreatable pain conditions.
Veterinary Anaesthesia and Analgesia, 2012
To assess the effect of adjunctive gabapentin (GBP) on pain after thoracolumbar intervertebral disc surgery in dogs. Prospective, randomized, controlled, clinical, 'blinded' trial. Sixty-three client owned dogs undergoing hemilaminectomy Dogs were assigned to two treatment groups. The GBP group received gabapentin 10 mg kg(-1) orally every 12 hours starting before anaesthesia; the placebo (P) group received empty gelatin capsules. Background analgesia was initiated with intravenous levomethadone 0.6 mg kg(-1) (as the combination 'L-Polamivet) at anaesthesia induction, followed by a fentanyl patch and levomethadone 0.2 mg kg(-1) subcutaneously every 8 hours for 24 hours. Pain was assessed by the short form of the Glasgow Composite Measure Pain Score (CMPS-SF) without the gait category, and by a Visual Analogue Scale (VAS). Serum GBP concentrations and cortisol concentrations were measured. Statistical analyses utilized chi square test, Kolmogorov-Smirnov test, two-way analysis of variances for repeated measurements, Wilcoxon test and Friedmann test as relevant. Correlations were tested by Spearman's and Pearson's correlation coefficient. p < 0.05 was considered significant. Median CMPS-SF was lower in group GBP than in group P on days 0.5, 1, 4 and 5. However, CMPS-SF and VAS were not significantly different between groups. Both pain scores decreased significantly over time. Cortisol concentrations were not significantly different between groups. Minimum serum concentrations of GBP fell below the detection limit of 1 μg mL(-1) in 6 of 29 and 7 of 28 dogs at 24 and 72 hours, respectively. 10 mg kg(-1) GBP orally twice a day did not result in a detectable reduction in pain behaviour compared to background opioid analgesia alone, although a trend to lower pain levels (p < 0.1) was present. Further studies are needed to determine if this is related to effective background analgesia or an ineffective dose of GBP.
Journal of the American Veterinary Medical Association, 2010
Scientific Reports 751 SMALL ANIMALS/ EXOTIC M anagement of postoperative pain is one of the major challenges of veterinary medicine. Classes of analgesics commonly used in dogs include opioids and NSAIDs, which may be associated with adverse effects such as sedation, dysphoria, gastrointestinal tract dysfunction, or renal toxicosis. For this reason, adjunct analgesic techniques that have the potential to improve comfort without adverse effects are of interest. For example, subanesthetic doses of ketamine can improve postoperative pain scores and activity in dogs undergoing amputation of a forelimb. 1 Gabapentin, a medication originally developed for use as an anticonvulsant, has received considerable attention in the human literature for its ability to decrease chronic neuropathic pain (often related to cancer) 2,3 and, more recently, to decrease acute postoperative pain. 4-8 Gabapentin is an alkylated GABA analogue that may modulate pain through binding to α2δ calcium channel
International Journal of Research in Medical Sciences, 2016
Pain is an unpleasant, sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage. 1 Pain could be acute or chronic in nature. Acute pain is short lasting and easy to manage while chronic pain is that pain which persists beyond the usual course of injury or diseases, or reoccurs in every few months or years. Pathologically chronic pain could be inflammatory or neuropathic. Inflammatory pain is due to chronic inflammation that is increased by pressure, but neuropathic pain occurs due to alteration in nervous system function or reorganization of nervous system structure and are non-adaptable. NSAIDs and opioids are the most potent and commonly used group of established analgesic drugs in treatment of pain, but there use is associated with a greater degree of adverse drug reactions and abuse liability. 2 The anticonvulsants carbamazepine and gabapentine are now established drugs for trigeminal neuralgia and postoperative pain as non conventional analgesics. 3 Other ABSTRACT Background: Some antiepileptic drugs have been shown to be clinically efficacious in treatment of neuropathic pain and are being used by clinicians. This study is proposed to evaluate the efficacy of these drugs as compared to conventional analgesics. Methods: Formalin test has been used as the model of acute and chronic inflammatory pain. Formalin has been characterized by the occurrence of two characteristic phases of increased pain sensitivity in rats. The test drugs have been administered orally and scored according to a pain scale. Pain has been quantified by counting the incidence of spontaneous flinches, shakes and jerks of the formalin injected paw. Analgesic response or protection has been indicated if both paws are resting on floor with no obvious favouring of injected paw. Treatment group was compared with appropriate control groups using "student t test". Results: Per oral administration of gabapentin produced no any marked effect on early phase response of formalin test but significantly suppressed the late phase response while diclofenac produced significant antinociceptive effect in both phases of formalin test. Conclusions: Thus we have observed that gabapentin produced antinociception in second phase of formalin test which reflects chronic inflammatory pain.
Gabapentin is Effective in Visceral Biphasic Animal Pain Models: An Experimental Study
Journal of Pharmaceutical & Scientific Innovation, 2015
Pain syndrome involves a variety of etiopathogenesis and temporal domains, management of pain as such requires consideration of many factors that may dictate appropriate therapeutic management. Carabmazepine is an established drug for trigeminal neuralgia while Gabapentin has been tried in postoperative pain but its effectiveness perse and when compared to conventional analgesics needs to be evaluated. The present study was planned to study the analgesic effects of Gabapentin in various pain models like writhing and formalin test and to compare it with conventional analgesics like Diclofenac sodium and Tramadol in various acute pain models. This study has been carried out in department of Pharmacology, HIMS, Dehradun, for evaluation of Gabapentin for its antinociceptive effect in rats and mice. In the writhing test, a reduction in number of writhes, though insignificant, was found in the Gabapentin pre-treatment group. However, in the first phase of Formalin test which is characterized by licking and biting, Gabapentin produced no significant effect in comparison to control values. In the second phase of leg raising (LR), all three drugs, i.e. Gabapentin and the two positive controls i.e. diclofenac and tramadol produced significant decrease (p < 0.05) in episodes when compared to the control group.
Gabapentin for once-daily treatment of post-herpetic neuralgia: a review
Clinical Interventions in Aging, 2012
Post-herpetic neuralgia is a neuropathic pain syndrome resulting from an insult to the peripheral and central nervous systems caused by the varicella zoster virus. Spontaneous pain may result in the persistent sensation of burning, tingling, or aching and may be associated with thermally or mechanically provoked pain, resulting in hyperalgesia or allodynia. The majority of cases occur in patients over the age of 50 years. Gabapentin is a structural analog of gamma aminobutyric acid that binds to the α 2 -δ site of voltage-dependent calcium channels and modulates the influx of calcium, with a resulting reduction in excitatory neurotransmitter release. Gabapentin is effective in reducing neuropathic pain due to post-herpetic neuralgia when given at least three times per day, due to its short half-life, resulting in demonstrable fluctuations in plasma levels. Gabapentin has dose-limiting side effects that prevent some patients from achieving therapeutic plasma levels, such as somnolence (27.4%), dizziness (23.9%), and ataxia (7.1%). Gralise™ is a once-daily extended-release formulation of gabapentin that has been developed using AcuForm™ technology. AcuForm is a polymer-based drug delivery system that retains the tablet in the stomach and upper gastrointestinal tract for a sustained period of time. Once-daily dosing has been shown to provide comparable drug exposure with an identical daily dose of the immediate-release formulation when administered three times daily. Participants given Gralise 1800 mg daily had a statistically significant reduction in average daily pain intensity scores compared with placebo, reduced sleep interference due to pain, and a greater percent of participants reporting being much or very much improved on the patient global impression of change. An analysis comparing the efficacy and safety profiles in the aging population ($65 years) with those younger than 65 years showed that Gralise is effective and well tolerated in both age groups.
Pharmacokinetics of oral gabapentin in greyhound dogs
The Veterinary Journal, 2011
The purpose of this study was to assess the pharmacokinetics of gabapentin in healthy Greyhound dogs after single oral doses targeted at 10 and 20 mg/kg PO. Six healthy Greyhounds were enrolled (3 males, 3 females). Blood was obtained at predetermined times for the measurement of gabapentin plasma concentrations by liquid chromatography/mass spectrometry. Pharmacokinetic parameters were determined with computer software. The actual mean (and range) doses administered were 10.2 (9.1-12.0) mg/kg and 20.5 (18.2-24) mg/kg for the 10 mg/kg and 20 mg/kg targeted dose groups. The mean C MAX for the 10 and 20 mg/kg groups were 8.54 and 13.22 μg/mL at 1.3 and 1.5 h, and the terminal half-lives were 3.3 and 3.4 h, respectively. The relative bioavailability of the 10 mg/kg group was 1.13 compared to the 20 mg/kg group. Gabapentin was rapidly absorbed and eliminated in dogs indicating frequent dosing is needed to maintain minimum targeted plasma concentrations.
Gabapentin: pharmacology and its use in pain management
Anaesthesia, 2002
Although its exact mode of action is not known, gabapentin appears to have a unique effect on voltage-dependent calcium ion channels at the postsynaptic dorsal horns and may, therefore, interrupt the series of events that possibly leads to the experience of a neuropathic pain sensation. Gabapentin is especially effective at relieving allodynia and hyperalgesia in animal models. It has been shown to be ef®cacious in numerous small clinical studies and case reports in a wide variety of pain syndromes. Gabapentin has been clearly demonstrated to be effective for the treatment of neuropathic pain in diabetic neuropathy and postherpetic neuralgia. This evidence, combined with its favourable side-effect pro®le in various patient groups (including the elderly) and lack of drug interactions, makes it an attractive agent. Therefore, gabapentin should be considered an important drug in the management of neuropathic pain syndromes.
Gabapentin as an adjuvant for postoperative pain management in dogs undergoing mastectomy
The Journal of veterinary medical science / the Japanese Society of Veterinary Science, 2015
This study aimed to evaluate the analgesic efficacy of gabapentin as an adjuvant for postoperative pain management in dogs. Twenty dogs undergoing mastectomy were randomized to receive perioperative oral placebo or gabapentin (10 mg/kg). All dogs were premedicated with intramuscular acepromazine (0.03 mg/kg) and morphine (0.3 mg/ kg). Anesthesia was induced with propofol (4 mg/kg) intravenously and maintained with isoflurane. Intravenous meloxicam (0.2 mg/kg) was administered preoperatively. Postoperative analgesia was evaluated for 72 hr. Rescue analgesia was provided with intramuscular morphine (0.5 mg/kg). Dogs in the Placebo group received significantly more morphine doses than the Gabapentin group (P=0.021) despite no significant differences in pain scores. Perioperative gabapentin reduced the postoperative morphine requirements in dogs after mastectomy.
Journal of Veterinary Behavior, 2019
Degenerative lumbosacral stenosis is a relatively common multifactorial disease that affects mainly large breed or working dogs. It can cause neuropathic pain, and advanced imaging techniques are essential to achieve a final diagnosis. For improving the quality of life, when surgery is not possible, a conservative treatment is necessary. The management of pain requires early intervention and evaluation of response on an individual-patient basis. The aim of the study was to evaluate the use of tramadol for the treatment of lumbosacral pain in dogs affected by degenerative lumbosacral stenosis diagnosed by radiographs, computed tomography, and computed tomography myelography, considering gabapentin as an alternative treatment in case of unresponsiveness. Ten dogs were enrolled, and clinical findings and their severity scores were recorded; the short form of the Glasgow composite pain scale was used to assess pain scores before (8.6 AE 1.5; 7-11/20) and during treatment (after 1, 2, and 4 weeks) with oral tramadol (3 mg/Kg every 8 hours) and prednisolone (0.5 mg/Kg/die) for 4 weeks. After the first week of therapy, only half of the dogs (5/10, T-group) showed a significant improvement of Glasgow composite pain scale score; in the remaining five dogs (G-group), tramadol was changed with oral gabapentin (10 mg/Kg every 8 hours for 3 weeks), with an improvement in pain score in one week. At the end of treatment, all the dogs showed low pain scores (T-group: 2.8 AE 0.8; G-group: 1.6 AE 0.9), below the intervention level (4/ 20). Given the supported evidence, oral tramadol should not be relied on as a sole or, perhaps, first-line analgesic in dogs, and gabapentin might be a valid alternative option in an outpatient setting. As controlled clinical trials are still lacking in animals, further studies should be carried out to confirm the analgesic activity of gabapentin in veterinary painful conditions and to rule out eventual adverse effects related to a prolonged administration.