Conditioned Place Preference Reveals Tonic Pain in an Animal Model of Central Pain

Davoody, Leyla; Quiton, Raimi L.; Lucas, Jessica M.; Ji, Yadong; Keller, Asaf; Masri, Radi

doi:10.1016/j.jpain.2011.01.010

Cited by 73 publications

(74 citation statements)

References 40 publications

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“…Therefore, assessment of wellbeing and functional rehabilitation should also be included in tbe screening process of analgesic drugs at tbe preclinical level. Accordingly, improved but more complex approaches have recently been proposed to measure pain and its effects, like conditioned place preference/aversion paradigms (53,(82)(83)(84)(85)(86)(87)88), rat grimace scale (89), or spontaneous innate bebaviors {e.g., burrowing; refs. 90,91).…”

Section: Discussionmentioning

confidence: 99%

Spinal NTS2 receptor activation reverses signs of neuropathic pain

Tétreault¹,

Beaudet²,

Perron

et al. 2013

FASEB j.

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Management of painful peripheral neuropathies remains challenging, since patients with chronic pain respond poorly to the available pharmacopeia. In recent years, the G-protein-coupled receptor neurotensin (NT) type 2 (NTS2) emerged as an attractive target for treating transitory pain states. To date, however, there is no evidence for its role in the regulation of chronic peripheral neuropathies. Here, we found that NTS2 receptors were largely localized to primary afferent fibers and superficial dorsal horns. Changes in the time course of the gene expression profile of NT, NTS1, and NTS2 were observed over a 28-d period following the sciatic nerve constriction [chronic constriction injury (CCI) model]. We next determined the effects of central delivery of selective-NTS2 agonists to CCI-treated rats on both mechanical allodynia (evoked withdrawal responses) and weight-bearing deficits (discomfort and quality-of-life proxies). The NTS2 analogs JMV431, levocabastine, and β-lactotensin were all effective in reducing ongoing tactile allodynia in CCI-treated rats. Likewise, amitriptyline, pregabalin, and morphine significantly attenuated CCI-induced mechanical hypersensitivity. NTS2 agonists were also efficient in reversing weight-bearing and postural deficits caused by nerve damage, unlike reference analgesics currently used in the clinic. Thus, NTS2 agonists may offer new treatment avenues for limiting pain associated with peripheral neuropathies and improve functional rehabilitation and well-being.

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Section: Discussionmentioning

confidence: 99%

Spinal NTS2 receptor activation reverses signs of neuropathic pain

Tétreault¹,

Beaudet²,

Perron

et al. 2013

FASEB j.

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“…We used CPP test to investigate whether DSS treatment induced ongoing abdominal discomfort/aversive state. As previously shown in models of neuropathic or chronic inflammatory pain, relief of pain/discomfort by analgesic treatment is rewarding and reinforces behaviors associated with the treatment (11,18). We infused the colon with 2% lidocaine jelly to impair afferent nerve activity, and we assessed the ability of control and DSS rats to associate analgesic treatment with a chamber providing relief.…”

Section: Spontaneous Activity and Sensitization Of Afferent Neurons Bmentioning

confidence: 95%

Genesis of anxiety, depression, and ongoing abdominal discomfort in ulcerative colitis-like colon inflammation

Chen

Winston

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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of anxiety, depression, and ongoing abdominal discomfort in ulcerative colitis-like colon inflammation. Am J Physiol Regul Integr Comp Physiol 308: R18-R27, 2015. First published November 1, 2014; doi:10.1152/ajpregu.00298.2014.-Psychological disorders are prevalent in patients with inflammatory bowel disease; the underlying mechanisms remain unknown. We tested the hypothesis that ulcerative colitis-like inflammation induced by dextran sodium sulfate (DSS) exacerbates the ongoing spontaneous activity in colon-projecting afferent neurons that induces abdominal discomfort and anxiety, and depressive-like behaviors in rats. In this study, we used the conditioned place preference and standard tests for anxiety-and depression-like behaviors. DSS rats developed anxiety-and depression-like behaviors 10 to 20 days after the start of inflammation. Single-fiber recordings showed an increase in the frequency of spontaneous activity in L6-S1 dorsal root ganglion (DRG) roots. Prolonged desensitization of transient receptor potential vanilloid 1 (TRPV1)-expressing colonic afferents by resiniferatoxin (RTX) suppressed the spontaneous activity, as well as the anxiety-and depressive-like behaviors. Reduction in spontaneous activity in colon afferents by intracolonic administration of lidocaine produced robust conditioned place preference (CPP) in DSS rats, but not in control rats. Patchclamp studies demonstrated a significant decrease in the resting membrane potential, lower rheobase, and sensitization of colonprojecting L6-S1 DRG neurons to generate trains of action potentials in response to current injection in DSS rats. DSS inflammation upregulated the mRNA levels of transient receptor potential ankyrin 1 and TRPV1 channels and downregulated that of K v1.1 and Kv1.4 channels. Ulcerative colitis-like inflammation in rats induces anxietyand depression-like behaviors, as well as ongoing abdominal discomfort by exacerbating the spontaneous activity in the colon-projecting afferent neurons. Alterations in the expression of voltage-and ligandgated channels are associated with the induction of mood disorders following colon inflammation.inflammatory bowel disease; spontaneous activity in visceral afferent neurons; anxiety; depression; visceral hypersensitivity ACCUMULATING EVIDENCE SHOWS that peripheral inflammation in chronic diseases, including Type 1 diabetes, cardiovascular disease, asthma, rheumatoid arthritis, chronic pulmonary disease, and chronic hepatitis C, associates with anxiety and depression in vulnerable patients (7). Inflammatory bowel disease (IBD) causes intense overt inflammation in the distal gut. The prevalence of psychological disorders is controversial in IBD patients (20). However, various reports show that as high as 80% of IBD patients suffer from anxiety and 60% from depression during relapse (1) and 29% to 35% during remission (3, 22). The cellular and neurological mechanisms by which peripheral inflammation induces anxiety and depression remain unknown.Evoked pain induced by balloon distension in the col...

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“…Importantly, CPP has been demonstrated in injured rats following pain-relieving treatments that do not produce preference in uninjured animals. Thus, analgesic treatments including peripheral nerve block, intrathecal administration of ω-conotoxin or clonidine, or RVM lidocaine may become rewarding in the presence of ongoing pain 31,34,67,72,74 . This conclusion is consistent with the concept of negative reinforcement elicited by relief of an aversive state.…”

Section: Preclinical Measures Of Pain Affectmentioning

confidence: 99%

“…The difference score, calculated as increased time spent in the drug-paired chamber on test day compared to the day before conditioning, indicates preference for the drug treatment. Single-trial protocols are appropriate when the treatments employed produce rapid change in pain affect (for example, peripheral nerve block, intrathecal clonidine, RVM lidocaine, electrical stimulation of motor cortex) 67,72,74 . The effects of slow-acting drugs can be revealed if the drug is given as a pretreatment that may produce relief of the pain-induced aversive state and prevent CPP to a rapidly acting pain reliever.…”

Section: Modulation Of Pain and Reward/motivation Pathwaysmentioning

confidence: 99%

Reward and motivation in pain and pain relief

2014

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Pain is fundamentally unpleasant, a feature that protects the organism by promoting motivation and learning. Relief of aversive states, including pain, is rewarding. The aversiveness of pain, as well as the reward from relief of pain, is encoded by brain reward/motivational mesocorticolimbic circuitry. In this Review, we describe current knowledge of the impact of acute and chronic pain on reward/motivation circuits gained from preclinical models and from human neuroimaging. We highlight emerging clinical evidence suggesting that anatomical and functional changes in these circuits contribute to the transition from acute to chronic pain. We propose that assessing activity in these conserved circuits can offer new outcome measures for preclinical evaluation of analgesic efficacy to improve translation and speed drug discovery. We further suggest that targeting reward/motivation circuits may provide a path for normalizing the consequences of chronic pain to the brain, surpassing symptomatic management to promote recovery from chronic pain.

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Conditioned Place Preference Reveals Tonic Pain in an Animal Model of Central Pain

Cited by 73 publications

References 40 publications

Spinal NTS2 receptor activation reverses signs of neuropathic pain

Spinal NTS2 receptor activation reverses signs of neuropathic pain

Genesis of anxiety, depression, and ongoing abdominal discomfort in ulcerative colitis-like colon inflammation

Reward and motivation in pain and pain relief

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