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

Abstract

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.

Pain-Related Depression of the Mesolimbic Dopamine System in Rats: Expression, Blockade by Analgesics, and Role of Endogenous κ-opioids

“…This study extended previous findings by using a higher intensity noxious stimulus (5.6% vs 1.8% lactic acid, see below), and despite use of this higher intensity stimulus, both ketoprofen and morphine retained efficacy to block acid-induced depression of ICSS. These results also agree with previous studies showing painrelated and analgesic-reversible depression of other behaviors including feeding (Kwilasz and Negus, 2012;Stevenson et al, 2006), locomotion (Cobos et al, 2012;Stevenson et al, 2009), burrowing (Andrews et al, 2012), and positively reinforced operant responding (Martin et al, 2004).…”

“…The mechanisms of pain-related depression are not well understood. In preclinical studies, injury, disease, or treatment with experimental noxious stimuli can produce an analgesic-reversible depression of behaviors that include feeding (Kwilasz and Negus, 2012;Stevenson et al, 2006), locomotion (Cobos et al, 2012;Stevenson et al, 2009), burrowing (Andrews et al, 2012), and positively reinforced operant responding (Martin et al, 2004). For example, intracranial self-stimulation (ICSS) is an operant procedure in which subjects emit a learned response such as a lever press to earn pulses of electrical stimulation to brain reward areas (Carlezon and Chartoff, 2007;Olds and Milner, 1954).…”

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

“…Animals were acclimatized to the laboratory room for at least 1 h before the start of each of the behavioural experiments. (Bove et al, 2003;Andrews et al, 2012).…”

“…Studies have reported several diseases and health issues that impact on burrowing ability, including inflammatory pain using intraplantar injections of complete Freund's adjuvant (CFA) (Andrews et al, 2011(Andrews et al, , 2012, post-operative pain (Jirkof et al, 2010), prion disease (Deacon et al, 2001), and trauma to peripheral nerves (Kim and Chung, 1992;Lee et al, 2000;Andrews et al, 2012) and the central nervous system (Deacon et al, 2002(Deacon et al, , 2003. As such, burrowing is considered an effective measure of global well-being in rodents (Andrews et al, 2012). To reproducibly measure burrowing in rats and other rodents, a simple, low-cost quantitative burrowing assay was developed (Deacon, 2006(Deacon, , 2009.…”

Enhanced c‐Fos expression in the central amygdala correlates with increased thigmotaxis in rats with peripheral nerve injury

“…In animal models, the effect of nociceptive stimuli on the affective and cognitive experience can be approximated using ethologically relevant behaviours such as burrowing (Andrews et al., 2012) and thigmotaxis (Huang et al., 2013). Behavioural alterations have been described in rat models of peripheral traumatic nerve injury (Hu et al., 2007; Blackbeard et al., 2012; Galan‐Arriero et al., 2015; Wang et al., 2015; Avila‐Martin et al., 2015; Grégoire et al., 2012), neuropathic viral infection (Hasnie et al., 2007; Wallace et al., 2007a) and drug‐induced neuropathies (Wallace et al., 2007b; Huang et al., 2013).…”