Automated measurement of spontaneous pain‐associated limb movement and drug efficacy evaluation in a rat model of neuropathic pain

Kawasaki-Yatsugi, Sachiko; Nagakura, Yukinori; Ogino, Shuichi; Sekizawa, Tsuyoshi; Kiso, Tetsuo; Takahashi, M; Ishikawa, Go; Ito, Hiroyuki; Shimizu, Yoshiyuki

doi:10.1002/j.1532-2149.2012.00142.x

Cited by 22 publications

(14 citation statements)

References 43 publications

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“…Spontaneous pain-associated limb movement was measured as described previously (Kawasaki-Yatsugi et al, 2012). Briefly, a small polytetrafluoroethylene-coated columnar magnet (1 mm in diameter, 3 mm long) (SCT-MAG-TF; Neuroscience Inc., Tokyo, Japan) was implanted into the s.c. space of the left hind limb dorsum under isoflurane anesthesia.…”

Section: Methodsmentioning

confidence: 99%

AS1069562, the (+)-Isomer of Indeloxazine, Exerts Analgesic Effects in a Rat Model of Neuropathic Pain with Unique Characteristics in Spinal Monoamine Turnover

Murai

Aoki

Tamura

et al. 2013

J Pharmacol Exp Ther

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AS1069562 [(R)-2-[(1H-inden-7-yloxy)methyl]morpholine monobenzenesulfonate] is the (1)-isomer of indeloxazine, which had been used clinically for the treatment of cerebrovascular diseases with multiple pharmacological actions, including serotonin (5-HT) and norepinephrine (NE) reuptake inhibition. Here we investigated the analgesic effects of AS1069562 in a rat model of chronic constriction injury (CCI)-induced neuropathic pain and the spinal monoamine turnover. These effects were compared with those of the antidepressants duloxetine and amitriptyline. AS1069562 significantly elevated extracellular 5-HT and NE levels in the rat spinal dorsal horn, although its 5-HT and NE reuptake inhibition was much weaker than that of duloxetine in vitro. In addition, AS1069562 increased the ratio of the contents of both 5-HT and NE to their metabolites in rat spinal cord, whereas duloxetine slightly increased only the ratio of the content of 5-HT to its metabolite. In CCI rats, AS1069562 and duloxetine significantly ameliorated mechanical allodynia, whereas amitriptyline did not. AS1069562 and amitriptyline significantly ameliorated thermal hyperalgesia, and duloxetine tended to ameliorate it. Furthermore, AS1069562, duloxetine, and amitriptyline significantly improved spontaneous pain-associated behavior. In a gastric emptying study, AS1069562 affected gastric emptying at the same dose that exerted analgesia in CCI rats. On the other hand, duloxetine and amitriptyline significantly reduced gastric emptying at lower doses than those that exerted analgesic effects. These results indicate that AS1069562 broadly improved various types of neuropathic pain-related behavior in CCI rats with unique characteristics in spinal monoamine turnover, suggesting that AS1069562 may have potential as a treatment option for patients with neuropathic pain, with a different profile from currently available antidepressants.

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Section: Methodsmentioning

confidence: 99%

AS1069562, the (+)-Isomer of Indeloxazine, Exerts Analgesic Effects in a Rat Model of Neuropathic Pain with Unique Characteristics in Spinal Monoamine Turnover

Murai

Aoki

Tamura

et al. 2013

J Pharmacol Exp Ther

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show abstract

“…To test whether the application of GABA evoked a nociception, we performed behavioral tests for each chemical. Mouse hindpaw movements indicating pain, i.e., lifting/guarding, flinching/shaking, licking, and walking (Kawasaki-Yatsugi et al, 2012), significantly increased after subcutaneous injection of capsaicin or KCl ( Ps < 0.001 vs. vehicle). On the other hand, GABA induced no significant increase ( P = 0.693; Figure 1D), indicating that GABA could not induce nociception.…”

Section: Resultsmentioning

confidence: 99%

“…Immediately after injection, mice were returned to the glass floor cage and 5 min video recordings were made. The number of movements of the injected limb, including lifting/guarding, flinching/shaking, licking, and walking, was determined by visual observation and considered as an indication of pain (Kawasaki-Yatsugi et al, 2012). …”

Section: Methodsmentioning

confidence: 99%

Analysis of Nociceptive Information Encoded in the Temporal Discharge Patterns of Cutaneous C-Fibers

Cho

Jang

Kim

et al. 2016

Front. Comput. Neurosci.

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The generation of pain signals from primary afferent neurons is explained by a labeled-line code. However, this notion cannot apply in a simple way to cutaneous C-fibers, which carry signals from a variety of receptors that respond to various stimuli including agonist chemicals. To represent the discharge patterns of C-fibers according to different agonist chemicals, we have developed a quantitative approach using three consecutive spikes. By using this method, the generation of pain in response to chemical stimuli is shown to be dependent on the temporal aspect of the spike trains. Furthermore, under pathological conditions, gamma-aminobutyric acid resulted in pain behavior without change of spike number but with an altered discharge pattern. Our results suggest that information about the agonist chemicals may be encoded in specific temporal patterns of signals in C-fibers, and nociceptive sensation may be influenced by the extent of temporal summation originating from the temporal patterns.

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“…In addition to differences in the time-course of effects on operant escape and flexion/withdrawal reflexes, several discrepancies are noted for bilateral vs. unilateral CCI: (A) Spontaneous behaviors such as guarding have been observed following unilateral CCI, and this is presumed to be indicative of ongoing pain (Attal et al, 1994;Kawasaki-Yatsugi et al, 2012;Mao et al, 1993). However, spontaneous behaviors were not observed following bilateral sciatic ligation.…”

Section: Laboratory Animal Models Of Neuropathic Pain Following Peripmentioning

confidence: 88%

Comparison of operant escape and reflex tests of nociceptive sensitivity

Vierck

Yezierski

2015

Neuroscience & Biobehavioral Reviews

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Automated measurement of spontaneous pain‐associated limb movement and drug efficacy evaluation in a rat model of neuropathic pain

Cited by 22 publications

References 43 publications

AS1069562, the (+)-Isomer of Indeloxazine, Exerts Analgesic Effects in a Rat Model of Neuropathic Pain with Unique Characteristics in Spinal Monoamine Turnover

AS1069562, the (+)-Isomer of Indeloxazine, Exerts Analgesic Effects in a Rat Model of Neuropathic Pain with Unique Characteristics in Spinal Monoamine Turnover

Analysis of Nociceptive Information Encoded in the Temporal Discharge Patterns of Cutaneous C-Fibers

Comparison of operant escape and reflex tests of nociceptive sensitivity

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