Rationale: The robust advances in pain management for companion animals underlie the decision of the American Animal Hospital Association (AAHA) and American Association of Feline Practitioners (AAFP) to expand on the information provided in the 2007 AAHA/AAFP Pain Management Guidelines. The 2015 Guidelines summarize and offer a discriminating review of much of this new knowledge. Relevance: Pain management is central to veterinary practice, alleviating pain, improving patient outcomes, and enhancing both quality of life and the veterinarian‐client‐patient relationship. These Guidelines support veterinarians in incorporating pain management into practice, improving patient care. Approaches: The management of pain requires a continuum of care that includes anticipation, early intervention, and evaluation of response on an individual patient basis. A team-oriented approach, including the owner, is essential for maximizing the recognition, prevention and treatment of pain in animals. Evidence base: The Guidelines include both pharmacologic and non-pharmacologic modalities to manage pain; they are evidence-based insofar as possible and otherwise represent a consensus of expert opinion. Behavioral changes are currently the principal indicator of pain and its course of improvement or progression, and the basis for recently validated pain scores. Post-surgical pain is eminently predictable but a strong body of evidence exists supporting strategies to mitigate adaptive as well as maladaptive forms. Chronic pain is dominated by degenerative joint disease (DJD), which is one of the most significant and under-diagnosed diseases of cats and dogs. DJD is ubiquitous, found in pets of all ages, and inevitably progresses over time; evidence-based strategies for management are established in dogs, and emerging in cats.

/pdf/2015-aaha-aafp-pain-management-guidelines-for-dogs-and-cats-52ov3lm2de.pdf

2015 AAHA/AAFP Pain Management Guidelines for Dogs and Cats*

In this study, histopathological and biochemical changes due to chronic usage of morphine or tramadol in liver and kidney were assessed in rats. Thirty male Wistar rats (180–220 g) were included and divided into three groups. Normal saline (1 ml) was given intraperitoneally as placebo in the control group (n = 10). Morphine group (n = 10) received morphine intraperitoneally at a dose of 4, 8, 10 mg/kg/day in the first, second and the third ten days of the study, respectively. Tramadol group (n = 10), received the drug intraperitoneally at doses of 20, 40 and 80 mg/kg/day in the first, second and the third ten days of the study, respectively. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatinin, blood urea nitrogen (BUN) and malondialdehyde (MDA) levels were measured in the serum. Liver and kidney specimens were evaluated by light microscopy. Serum ALT, AST, LDH, BUN and creatinin levels were significantly higher in morphine group compared to the control group. Serum LDH, BUN and creatinin levels were significantly increased in the morphine group compared to the tramadol group. The mean MDA level was significantly higher in morphine group compared to the tramadol and control groups (P<0.05). Light microscopy revealed severe centrolobular congestion and focal necrosis in the liver of morphine and tramadol groups, but perivenular necrosis was present only in the morphine group. The main histopathologic finding was vacuolization in tubular cells in morphine and tramadol groups. Our findings pointed out the risk of increased lipid peroxidation, hepatic and renal damage due to long term use of opioids, especially morphine. Although opioids are reported to be effective in pain management, their toxic effects should be kept in mind during chronic usage

Liver and kidney toxicity in chronic use of opioids: An experimental long term treatment model

In vitro genotoxicity testing needs to include tests in both bacterial and mammalian cells, and be able to detect gene mutations, chromosomal damage and aneuploidy. This may be achieved by a combination of the Ames test (detects gene mutations) and the in vitro micronucleus test (MNvit), since the latter detects both chromosomal aberrations and aneuploidy. In this paper we therefore present an analysis of an existing database of rodent carcinogens and a new database of in vivo genotoxins in terms of the in vitro genotoxicity tests needed to detect their in vivo activity. Published in vitro data from at least one test system (most were from the Ames test) were available for 557 carcinogens and 405 in vivo genotoxins. Because there are fewer publications on the MNvit than for other mammalian cell tests, and because the concordance between the MNvit and the in vitro chromosomal aberration (CAvit) test is so high for clastogenic activity, positive results in the CAvit test were taken as indicative of a positive result in the MNvit where there were no, or only inadequate data for the latter. Also, because Hprt and Tk loci both detect gene-mutation activity, a positive Hprt test was taken as indicative of a mouse-lymphoma Tk assay (MLA)-positive, where there were no data for the latter. Almost all of the 962 rodent carcinogens and in vivo genotoxins were detected by an in vitro battery comprising Ames+MNvit. An additional 11 carcinogens and six in vivo genotoxins would apparently be detected by the MLA, but many of these had not been tested in the MNvit or CAvit tests. Only four chemicals emerge as potentially being more readily detected in MLA than in Ames+MNvit--benzyl acetate, toluene, morphine and thiabendazole--and none of these are convincing cases to argue for the inclusion of the MLA in addition to Ames+MNvit. Thus, there is no convincing evidence that any genotoxic rodent carcinogens or in vivo genotoxins would remain undetected in an in vitro test battery consisting of Ames+MNvit.

A core in vitro genotoxicity battery comprising the Ames test plus the in vitro micronucleus test is sufficient to detect rodent carcinogens and in vivo genotoxins.

The atypical opioid, tramadol, has recently been introduced into Australia and New Zealand. Tramadol's efficacy in a wide range of acute and chronic pain states, its multi-formulation availability, and its low serious side-effect potential at high doses and in prolonged therapy, combine to bestow on it a user-friendly profile, for short- and long-term use in hospitals and communities. This paper reviews the following: its formulation and routes of administration; its unique enantiomeric biochemistry and metabolism; its triple mechanisms of action; its pharmacokinetics and pharmacodynamics; its analgesic efficacy compared with other opioids; the indications for its clinical use in a variety of acute and chronic (including cancer) painful states; its specific use in the elderly, in paediatric and in obstetric patients; its adverse event (including drug interaction) and safety profile; its advantages in terms of its relative lack of respiratory depression, major organ toxicity and histamine release, and dependence and abuse potential. The review looks at new uses for this drug and what can be expected in this area in the future.

Tramadol--present and future.

http://www.if-pan.krakow.pl/pjp/pdf/2009/6_978.pdf

T.P Coogan

Papers

The experimental toxicology of tramadol: an overview