Spontaneous burrowing behaviour in the rat is reduced by peripheral nerve injury or inflammation associated pain

Pain influences many aspects of daily living and effective analgesics should reinstate normal spontaneous daily behaviours. Experiments are described herein which show that the innate, spontaneous behaviour of burrowing by rats, which can be simply and objectively assessed by measuring the amount of gravel left in a hollow tube 1 h after presentation to the rat, is reduced by peripheral nerve injury (tibial nerve transection (TNT), L5 spinal nerve transection (SNT) and partial sciatic nerve ligation (PSNL)) and also following inflammation induced by intra‐plantar injection of Complete Freund's Adjuvant (CFA). Gabapentin (100 mg/kg sc) but not at 30 mg/kg sc significantly reduced burrowing activity in naive rats. All peripheral nerve injuries and CFA reduced burrowing compared with shams and rats naive to surgery. The level of mechanical hypersensitivity in rats with peripheral nerve injury did not correlate with the deficit in burrowing indicating that different parameters of the holistic pain experience are measured in these paradigms. Gabapentin at 30 mg/kg sc, but not 100 mg/kg sc, reversed the deficit in burrowing induced by TNT and ibuprofen (30 mg/kg sc) reversed the effect of CFA on burrowing. These experiments show that measurement of burrowing is a simple, objective assay of innate rodent behaviour affected by pain that is ethologically relevant to the rat, does not rely wholly on evoking a reflex and can dissociate a selective analgesic dose of gabapentin from one inducing motor impairment in the same animal.

[1]  Jin Mo Chung,et al.  An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat , 1992, PAIN.

[2]  R. Deacon Burrowing: A sensitive behavioural assay, tested in five species of laboratory rodents , 2009, Behavioural Brain Research.

[3]  P. Willner,et al.  The validity of animal models of depression , 2004, Psychopharmacology.

[4]  C. Argoff,et al.  Use of antiepileptic drugs for nonepileptic conditions: Psychiatric disorders and chronic pain , 2011, Neurotherapeutics.

[5]  B. Seifert,et al.  Burrowing Behavior as an Indicator of Post-Laparotomy Pain in Mice , 2010, Front. Behav. Neurosci..

[6]  Ronald Dubner,et al.  A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury , 1990, Pain.

[7]  A. Rice,et al.  Comparison of psychological and physical function in neuropathic pain and nociceptive pain: Implications for cognitive behavioral pain management programs , 2008, European journal of pain.

[8]  Wagner F. Gattaz,et al.  Pain perception threshold in major depression , 1993, Biological Psychiatry.

[9]  Glenn W. Stevenson,et al.  Targeting pain-suppressed behaviors in preclinical assays of pain and analgesia: effects of morphine on acetic acid-suppressed feeding in C57BL/6J mice. , 2006, The journal of pain : official journal of the American Pain Society.

[10]  F. Luo,et al.  The differential effects of depression on evoked and spontaneous pain behaviors in olfactory bulbectomized rats , 2010, Neuroscience Letters.

[11]  B. Lee,et al.  An animal model of neuropathic pain employing injury to the sciatic nerve branches , 2000, Neuroreport.

[12]  J. Mogil Animal models of pain: progress and challenges , 2009, Nature Reviews Neuroscience.

[13]  Stephen Pain,et al.  What is an Animal? , 2009, Biosemiotics.

[14]  J. Quinn,et al.  Behavioural changes in the rat following infection with varicella-zoster virus. , 1999, The Journal of general virology.

[15]  Gary J. Bennett,et al.  Studies of peripheral sensory nerves in paclitaxel-induced painful peripheral neuropathy: Evidence for mitochondrial dysfunction , 2006, Pain.

[16]  M. Zimmermann,et al.  Ethical guidelines for investigations of experimental pain in conscious animals , 1983, Pain.

[17]  R. Dworkin,et al.  Clinical aspects of depression in chronic pain patients. , 1991, The Clinical journal of pain.

[18]  H. Gould Complete Freund's adjuvant-induced hyperalgesia: a human perception , 2000, Pain.

[19]  F. Luo,et al.  Increased thermal and mechanical nociceptive thresholds in rats with depressive-like behaviors , 2010, Brain Research.

[20]  J. Davidson,et al.  Treatment of social phobia with gabapentin: a placebo-controlled study. , 1999, Journal of clinical psychopharmacology.

[21]  R. Deacon Burrowing in rodents: a sensitive method for detecting behavioral dysfunction , 2006, Nature Protocols.

[22]  Andrew R Segerdahl,et al.  Characterization of rodent models of HIV-gp120 and anti-retroviral-associated neuropathic pain. , 2007, Brain : a journal of neurology.

[23]  J. Rawlins,et al.  Age-dependent and -independent behavioral deficits in Tg2576 mice , 2008, Behavioural Brain Research.

[24]  J. Kehne,et al.  Inflammation-Induced Reduction of Spontaneous Activity by Adjuvant: A Novel Model to Study the Effect of Analgesics in Rats , 2007, Journal of Pharmacology and Experimental Therapeutics.

[25]  Andrew S.C. Rice,et al.  Animal models and the prediction of efficacy in clinical trials of analgesic drugs: A critical appraisal and call for uniform reporting standards , 2008, PAIN.

[26]  J. Breuer,et al.  Further characterization of a rat model of varicella zoster virus–associated pain: Relationship between mechanical hypersensitivity and anxiety-related behavior, and the influence of analgesic drugs , 2007, Neuroscience.

[27]  Karl-Jürgen Bär,et al.  Pain perception in major depression depends on pain modality , 2005, Pain.

[28]  V. Perry,et al.  Sub-pyrogenic systemic inflammation impacts on brain and behavior, independent of cytokines , 2007, Brain, Behavior, and Immunity.

[29]  T. Yaksh,et al.  Quantitative assessment of tactile allodynia in the rat paw , 1994, Journal of Neuroscience Methods.

[30]  V. Perry,et al.  Early behavioural changes in scrapie‐affected mice and the influence of dapsone , 2001, The European journal of neuroscience.

[31]  G. Woodruff,et al.  The antiepileptic agent gabapentin (Neurontin) possesses anxiolytic-like and antinociceptive actions that are reversed byd-serine , 1996, Psychopharmacology.

[32]  Colm Cunningham,et al.  The sickness behaviour and CNS inflammatory mediator profile induced by systemic challenge of mice with synthetic double-stranded RNA (poly I:C) , 2007, Brain, Behavior, and Immunity.

[33]  B. Stacey,et al.  Pain severity in diabetic peripheral neuropathy is associated with patient functioning, symptom levels of anxiety and depression, and sleep. , 2005, Journal of pain and symptom management.