Bilateral Chronic Constriction of the Sciatic Nerve: A Model of Long-term Cold Hyperalgesia

Vierck, Charles J.; Acosta-Rua, Antonio J.; Johnson, Richard D.

doi:10.1016/j.jpain.2005.03.003

Cited by 54 publications

(61 citation statements)

References 45 publications

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“…The movement away from reflex-based measures of pain into operant tasks is becoming more common in the field. Other groups have used non-reflex-based measures like examining meal duration 21,22,23 and thermal heat pain escape paradigms 24 (For a review of other pain measures we suggest our first reference 1 ). The OPAD is able to combine elements of these into a unified measure, the Lick/Face ratio, which examines food intake and the need to escape from painful stimuli.…”

Section: Discussionmentioning

confidence: 99%

Use of the Operant Orofacial Pain Assessment Device (OPAD) to Measure Changes in Nociceptive Behavior

Anderson

Mills

Nolan

et al. 2013

JoVE

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We present an operant system for the detection of pain in awake, conscious rodents. The Orofacial Pain Assessment Device (OPAD) assesses pain behaviors in a more clinically relevant way by not relying on reflex-based measures of nociception. Food fasted, hairless (or shaved) rodents are placed into a Plexiglas chamber which has two Peltier-based thermodes that can be programmed to any temperature between 7°C and 60 °C. The rodent is trained to make contact with these in order to access a reward bottle. During a session, a number of behavioral pain outcomes are automatically recorded and saved. These measures include the number of reward bottle activations (licks) and facial contact stimuli (face contacts), but custom measures like the lick/face ratio (total number of licks per session/total number of contacts) can also be created. The stimulus temperature can be set to a single temperature or multiple temperatures within a session. The OPAD is a high-throughput, easy to use operant assay which will lead to better translation of pain research in the future as it includes cortical input instead of relying on spinal reflex-based nociceptive assays.

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Section: Discussionmentioning

confidence: 99%

Use of the Operant Orofacial Pain Assessment Device (OPAD) to Measure Changes in Nociceptive Behavior

Anderson

Mills

Nolan

et al. 2013

JoVE

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“…Experimental protocols were approved by the University of Florida Institutional Animal Care and Use Committee. The CCI model of Bennett and Xie (1988) was used with a slight modification (Vierck et al, 2005). In brief, animals were anesthetized with continuous inhalation of isofluorane.…”

Section: Methodsmentioning

confidence: 99%

TRPM8 Mechanism of Cold Allodynia after Chronic Nerve Injury

Xiao¹,

Chen²,

Ling³

et al. 2007

J. Neurosci.

210

177

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The cold-and menthol-sensitive receptor TRPM8 (transient receptor potential melastatin 8) has been suggested to play a role in cold allodynia, an intractable pain seen clinically. We studied how TRPM8 is involved in cold allodynia using rats with chronic constrictive nerve injury (CCI), a neuropathic pain model manifesting cold allodynia in hindlimbs. We found that cold allodynic response in the CCI animals was significantly attenuated by capsazepine, a blocker for both TRPM8 and TRPV1 (transient receptor potential vanilloid 1) receptors, but not by the selective TRPV1 antagonist I-RTX (5-iodoresiniferatoxin). In L5 dorsal root ganglion (DRG) sections of the CCI rats, immunostaining showed an increase in the percentage of TRPM8-immunoreactive neurons when compared with the sham group. Using the Ca 2ϩ -imaging technique and neurons acutely dissociated from the L5 DRGs, we found that CCI resulted in a significant increase in the percentage of menthol-and cold-sensitive neurons and also a substantial enhancement in the responsiveness of these neurons to both menthol and innocuous cold. These changes occurred in capsaicin-sensitive neurons, a subpopulation of nociceptive-like neurons. Using patch-clamp recordings, we found that membrane currents evoked by both menthol and innocuous cold were significantly enhanced in the CCI group compared with the sham group. By retrograde labeling afferent neurons that target hindlimb skin, we showed that the skin neurons expressed TRPM8 receptors, that the percentage of menthol-sensitive/cold-sensitive/capsaicin-sensitive neurons increased, and that the menthol-and cold-evoked responses were significantly enhanced in capsaicin-sensitive neurons after CCI. Together, the gain of TRPM8-mediated cold sensitivity on nociceptive afferent neurons provides a mechanism of cold allodynia.

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“…Bilateral sciatic nerve chronic constriction injury (bCCI) is commonly used as a model for studying human neuropathic pain, in which chromic gut sutures are used to ligate each sciatic nerve. This model is characterized by long-lasting cold allodynia and mechanical hypersensitivity (25,26); however, no information is available on how miRNA expression patterns in the nociceptive system are altered.…”

Section: Introductionmentioning

confidence: 99%

Differential expression of miRNAs in the nervous system of a rat model of bilateral sciatic nerve chronic constriction injury

Shen

et al. 2013

International Journal of Molecular Medicine

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Abstract. Chronic neuropathic pain is associated with global changes in gene expression in different areas of the nociceptive pathway. MicroRNAs (miRNAs) are small (~22 nt long) noncoding RNAs, which are able to regulate hundreds of different genes post-transcriptionally. The aim of this study was to determine the miRNA expression patterns in the different regions of the pain transmission pathway using a rat model of human neuropathic pain induced by bilateral sciatic nerve chronic constriction injury (bCCI). Using microarray analysis and quantitative reverse transcriptase-PCR, we observed a significant upregulation in miR-341 expression in the dorsal root ganglion (DRG), but not in the spinal dorsal horn (SDH), hippocampus or anterior cingulate cortex (ACC), in the rats with neuropathic pain compared to rats in the naïve and sham-operated groups. By contrast, the expression of miR-203, miR-181a-1 * and miR-541 * was significantly reduced in the SDH of rats with neuropathic pain. Our data indicate that miR-341 is upregulated in the DRG, whereas miR-203, miR-181a-1 * and miR-541 * are downregulated in the SDH under neuropathic pain conditions. Thus, the differential expression of miRNAs in the nervous system may play a role in the development of chronic pain. These observations may aid in the development of novel treatment methods for neuropathic pain, which may involve miRNA gene therapy in local regions. IntroductionNeuropathic pain is defined as pain arising as a direct consequence of a lesion or disease affecting either the peripheral or central nervous system (1,2). Although pain has been investigated in depth for decades, neuropathic pain is still frequently under-treated (3), due to poor understanding of its pathophysiological and molecular mechanisms. Several regions of the nociceptive pathway, including the anterior cingulate cortex (ACC), hippocampus, spinal dorsal horn (SDH) and dorsal root ganglion (DRG), are involved in the development and maintenance of neuropathic pain (4-9). Several recent studies have shown that peripheral and central sensitization are associated with global changes in gene expression in different regions of the pain transmission pathway, and that these changes may be part of the mechanisms behind neuropathic pain (10-13). In order to elucidate the molecular mechanisms underlying neuropathic pain, it is essential to determine how gene expression patterns are altered by nerve injuries and how these alterations lead to the development and maintenance of chronic pain.miRNAs are a large class of short non-coding RNAs (~22 nt long), many of which are expressed either predominantly or exclusively in the nervous system (14-21). Furthermore, changes (either increases or decreases) in miRNA expression have been found in many disease states (22-24). Bilateral sciatic nerve chronic constriction injury (bCCI) is commonly used as a model for studying human neuropathic pain, in which chromic gut sutures are used to ligate each sciatic nerve. This model is characterized by long-lasting cold all...

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Bilateral Chronic Constriction of the Sciatic Nerve: A Model of Long-term Cold Hyperalgesia

Cited by 54 publications

References 45 publications

Use of the Operant Orofacial Pain Assessment Device (OPAD) to Measure Changes in Nociceptive Behavior

Use of the Operant Orofacial Pain Assessment Device (OPAD) to Measure Changes in Nociceptive Behavior

TRPM8 Mechanism of Cold Allodynia after Chronic Nerve Injury

Differential expression of miRNAs in the nervous system of a rat model of bilateral sciatic nerve chronic constriction injury

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