Animal models and the prediction of efficacy in clinical trials of analgesic drugs: A critical appraisal and call for uniform reporting standards

Rice, Andrew S.C.; Cimino-Brown, Dorothy; Eisenach, James C.; Kontinen, Vesa K.; LaCroix-Fralish, Michael L.; Ian, Machin; Mogil, Jeffrey S.; Stöhr, Thomas

doi:10.1016/j.pain.2008.08.017

Cited by 254 publications

(206 citation statements)

References 35 publications

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“…Animals were housed in a climate-controlled room on a 12-hour light/dark cycle, with water and standard rodent chow available ad libitum. All experiments were approved by the Thuringian state authorities and complied with European Union regulations (86/609/EEC) for the care and reporting standards for use of laboratory animals (20).…”

Section: Methodsmentioning

confidence: 99%

Differential antiinflammatory and antinociceptive effects of the somatostatin analogs octreotide and pasireotide in a mouse model of immune‐mediated arthritis

Imhof¹,

Glück²,

Gajda³

et al. 2011

Arthritis & Rheumatism

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Objective. Clinical and preclinical evidence suggests that somatostatin exhibits potent antiinflammatory and antinociceptive properties. However, it is not known which of the 5 somatostatin receptor subtypes (SSTRs 1-5) is involved in these actions. The purpose of this study was to assess the effects of the stable somatostatin analogs octreotide and pasireotide (SOM230) in a mouse model of antigen-induced arthritis (AIA). Methods. Studies were performed in SSTR2-deficient mice (SSTR2 -/-) and their wild-type littermates (SSTR2 ؉/؉). The expression of SSTR1, SSTR2A, SSTR3, and SSTR5 in dorsal root ganglia was examined by immunohistochemistry.Results. Untreated SSTR2 -/-mice with AIA displayed joint swelling and mechanical hyperalgesia similar to that seen in SSTR2 ؉/؉ mice. In wild-type mice, both octreotide and pasireotide significantly attenuated knee joint swelling and histopathologic manifestations of arthritis to an extent comparable to that of dexamethasone. In SSTR2 -/-mice, the antiinflammatory effects of both octreotide and pasireotide were completely abrogated. Prolonged administration of pasireotide also inhibited joint swelling and protected against joint destruction during AIA flare reactions. In addition, both octreotide and pasireotide reduced inflammatory hyperalgesia. The antinociceptive actions of octreotide were abolished in SSTR2 -/-mice, but those of pasireotide were retained. In dorsal root ganglia of naive wild-type mice, only SSTR1 and SSTR2A, but not SSTR3 or SSTR5, were detected in a subset of small-and mediumdiameter neurons.Conclusion. Our findings indicate that the antinociceptive and antiinflammatory actions of octreotide and pasireotide are largely mediated via the SSTR2 receptor. In addition, we identified the SSTR1 receptor as a novel pharmacologic target for somatostatinmediated peripheral analgesia in inflammatory pain.

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Section: Methodsmentioning

confidence: 99%

Differential antiinflammatory and antinociceptive effects of the somatostatin analogs octreotide and pasireotide in a mouse model of immune‐mediated arthritis

Imhof¹,

Glück²,

Gajda³

et al. 2011

Arthritis & Rheumatism

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“…Experiments were performed at the Department of Pharmacology Pain, Global Biomedical Sciences, Grünenthal GmbH, Aachen, Germany. The experiments are reported in concordance with the ARRIVE (Animal in Research: Reporting In Vivo Experiments) guidelines (Kilkenny et al, 2010), and an Extended Methods Form according to Rice et al (2008) accompanies this manuscript (see Supporting Information Appendix S1). Adult male Sprague Dawley rats (total n = 432; 175-199 g; Harlan Laboratories, Boxmeer, the Netherlands) were housed 5 per cage (Macrolon ® type IV, Tecniplast, Varese, Italy).…”

Section: Animalsmentioning

confidence: 98%

Burrowing as a non‐reflex behavioural readout for analgesic action in a rat model of sub‐chronic knee joint inflammation

Rutten¹,

Schiene²,

Robens³

et al. 2013

European Journal of Pain

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Background: Innate responses against spontaneous pain are proposed to improve the predictive validity of preclinical analgesia models. Therefore, development and validation of novel readouts is necessary. To investigate whether innate rodent burrowing is a useful alternative behavioural readout for assessment of analgesic efficacy, a complete Freund's adjuvant (CFA)-induced model of sub-chronic inflammation was used to compare the effects of naproxen, ibuprofen and pregabalin in weight-bearing (WB), open-field (OF) and burrowing assays. Methods: Male Sprague Dawley rats were injected with 150 μL of CFA (2 mg/mL) into the knee (hind leg) 3 days before testing. Naproxen, ibuprofen and pregabalin were administered at different doses 30, 90 and 60 min, respectively, before testing. WB was determined using a rat incapacitance tester; horizontal distance moved and vertical rearings were recorded in an OF; and burrowing was measured by the weight of gravel remaining in a hollow tube after 60 min. Results: CFA-induced arthritis reduced WB, OF activity and burrowing. Naproxen, pregabalin and ibuprofen treatment normalized WB; however, horizontal OF activity was not improved by any treatment; rearing behaviour was moderately reinstated by ibuprofen (100 mg/kg). In burrowing, naproxen (100 mg/kg), ibuprofen (31.6 and 100 mg/kg) and pregabalin (10 mg/kg) reversed CFA-induced deficits. Conclusions: Burrowing performance is an alternative non-reflex readout relying on innate rodent behaviour that is affected by nociceptive behaviour and can be pharmacologically manipulated. The burrowing assay appears to be more sensitive than OF assays and is as sensitive as WB assays at distinguishing between analgesic doses and doses that impair locomotion.

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“…Moreover, most novel medications are validated in animal models of traumatic neuropathy, whereas the evidence of NP efficacy is based on PHN, painful DPN, and other peripheral neuropathies. 78 Nevertheless, extrapolation of efficacy from first-line medications that have shown efficacy in one or more types of NP to other types of NP has seemed plausible, and medications that have shown efficacy in several different NP conditions may have the greatest probability of being efficacious in additional, as yet unstudied, conditions.…”

Section: Negative Trials Of Pharmacological Treatments For Np and Thementioning

confidence: 99%

Recommendations for the Pharmacological Management of Neuropathic Pain: An Overview and Literature Update

Dworkin

O’Connor

Audette

et al. 2010

Mayo Clinic Proceedings

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1,147

901

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The Neuropathic Pain Special Interest Group of the International Association for the Study of Pain recently sponsored the development of evidence-based guidelines for the pharmacological treatment of neuropathic pain. Tricyclic antidepressants, dual reuptake inhibitors of serotonin and norepinephrine, calcium channel a 2 -d ligands (ie, gabapentin and pregabalin), and topical lidocaine were recommended as first-line treatment options on the basis of the results of randomized clinical trials. Opioid analgesics and tramadol were recommended as second-line treatments that can be considered for first-line use in certain clinical circumstances. Results of several recent clinical trials have become available since the development of these guidelines. These studies have examined botulinum toxin, high-concentration capsaicin patch, lacosamide, selective serotonin reuptake inhibitors, and combination therapies in various neuropathic pain conditions. The increasing number of negative clinical trials of pharmacological treatments for neuropathic pain and ambiguities in the interpretation of these negative trials must also be considered in developing treatment guidelines. The objectives of the current article are to review the Neuropathic Pain Special Interest Group guidelines for the pharmacological management of neuropathic pain and to provide a brief overview of these recent studies.Mayo Clin Proc. 2010;85(3)(suppl):S3-S14 DPN = diabetic peripheral neuropathy; HIV = human immunodeficiency virus; HRQoL = health-related quality of life; NeuPSIG = Neuropathic Pain Special Interest Group; NP = neuropathic pain; PHN = postherpetic neuralgia; RCT = randomized clinical trial; SSNRI = selective serotonin norepinephrine reuptake inhibitor; SSRI = selective serotonin reuptake inhibitor; TCA = tricyclic antidepressant

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Animal models and the prediction of efficacy in clinical trials of analgesic drugs: A critical appraisal and call for uniform reporting standards

Cited by 254 publications

References 35 publications

Differential antiinflammatory and antinociceptive effects of the somatostatin analogs octreotide and pasireotide in a mouse model of immune‐mediated arthritis

Differential antiinflammatory and antinociceptive effects of the somatostatin analogs octreotide and pasireotide in a mouse model of immune‐mediated arthritis

Burrowing as a non‐reflex behavioural readout for analgesic action in a rat model of sub‐chronic knee joint inflammation

Recommendations for the Pharmacological Management of Neuropathic Pain: An Overview and Literature Update

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