Peripheral afferents and spinal inhibitory system in dynamic and static mechanical allodynia

La, Jun–Ho; Chung, Jin Mo

doi:10.1097/j.pain.0000000000001055

Cited by 27 publications

(18 citation statements)

References 59 publications

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“…Allodynia is classified as mechanical dynamic, mechanical static, and thermal allodynia. These types differ in terms of the transmission nerve fibres and nociceptors 30 , 31 . Each item of the ASC-12 comprised three types of CA.…”

Section: Discussionmentioning

confidence: 99%

Prevalence and characteristics of cutaneous allodynia in probable migraine

Han

Kim

Cho

et al. 2021

Sci Rep

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Cutaneous allodynia (CA) is a pain in response to non-nociceptive stimulation and a marker of central sensitisation. Probable migraine (PM) is a migraine subtype that fulfils all but one criterion of migraine. Headache intensity and the disability of individuals with PM are similar or lower than individuals with migraine. This study compared CA prevalence and characteristics of PM and migraine using a nationally representative sample in Korea. The Allodynia Symptom Checklist-12 (ASC-12) was used to assess CA (ASC-12 score ≥ 3). PM and migraine prevalence were 11.6% and 5.0%, respectively. CA prevalence did not significantly differ between PM and migraine (14.5% vs. 16.0%, p = 0.701). Participants with PM with CA reported a higher monthly headache frequency (3.3 ± 4.3 vs. 1.8 ± 3.6, p = 0.044), more severe headache intensity (Visuals Analogue Scale, 6.0 [4.0–7.0] vs. 5.0 [3.0–6.0], p = 0.002), and higher impact of headache (Headache Impact Test-6, 56.3 ± 7.2 vs. 48.3 ± 8.0, p < 0.001) than those without CA. Multiple regression analyses revealed that headache frequency and intensity, anxiety, and depression were significant factors for CA in participants with PM. In conclusion, CA prevalence among participants with PM and migraine were comparable. Anxiety, depression, and headache frequency and intensity were significant factors for CA in participants with PM.

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Section: Discussionmentioning

confidence: 99%

Prevalence and characteristics of cutaneous allodynia in probable migraine

Han

Kim

Cho

et al. 2021

Sci Rep

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“…Dynamic mechanical allodynia, the pain evoked by light brushing or stroking of the skin, is one of the most disabling symptoms of neuropathic pain. 3 , 28 Despite the recent progress in elucidating the underlying mechanisms, 4 , 29 , 30 effective treatment of dynamic allodynia remains elusive. 2 , 7 Many preclinical and clinical studies have identified ld-IL2 treatment as a safe and effective treatment for multiple autoimmune diseases, neurodegenerative diseases as well as chronic headache disorders through enhancing Treg-mediated immunosuppression.…”

Section: Discussionmentioning

confidence: 99%

Low-Dose Interleukin-2 and Regulatory T Cell Treatments Attenuate Punctate and Dynamic Mechanical Allodynia in a Mouse Model of Sciatic Nerve Injury

Hu¹,

Zhang²,

Liu³

et al. 2021

JPR

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Purpose Nerve injury-induced mechanical hyper-sensitivity, in particular stroking-induced dynamic allodynia, is highly debilitating and difficult to treat. Previous studies indicate that the immunosuppressive regulatory T (Treg) cells modulate the magnitude of punctate mechanical allodynia resulting from sciatic nerve injury. However, whether enhancing Treg-mediated suppression attenuates dynamic allodynia is not known. In the present study, we addressed this knowledge gap by treating mice with low-dose interleukin-2 (ld-IL2) injections or adoptive transfer of Treg cells. Methods Female Swiss Webster mice received daily injections of ld-IL2 (1 μg/mouse, intraperitoneally) either before or after unilateral spared nerve injury (SNI). Male C57BL/6J mice received adoptive transfer of 1 x 10 6 Treg cells 3 weeks post-SNI. The responses to punctate and dynamic mechanical stimuli on the hindpaw were monitored before and up to 4–6 weeks post-SNI. We also compared the distribution of Treg cells and CD3 + total T cells after SNI and/or ld-IL2 treatment. Results Ld-IL2 pretreatment in female Swiss Webster mice completely blocked the development of SNI-induced dynamic mechanical allodynia and reduced the magnitude of punctate allodynia. Delayed ld-IL2 treatment in female mice significantly attenuated the morphine-resistant punctate and dynamic allodynia at 3–5 weeks post-SNI. Adoptive transfer of Treg cells to male C57BL/6J mice 3 weeks post-SNI effectively reversed the persistent punctate and dynamic allodynia, supporting that the effect of ld-IL2 is mediated through endogenous Treg cells, and is likely independent of mouse strain and sex. Neither ld-IL2 treatment nor Treg transfer affected the basal responses to punctate or brush stimuli. Ld-IL2 significantly increased the frequency of Treg cells among total CD3 + T cells in the injured sciatic nerves but not in the uninjured nerves or the dorsal root ganglia, suggesting the injured nerve as ld-IL2’s site of action. Conclusion Collectively, results from the present study supports Treg as a cellular target and ld-IL2 as a potential therapeutic option for nerve injury-induced persistent punctate and dynamic mechanical allodynia.

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“…4 Different from punctate, different neural circuits were found to mediate the development of dynamic allodynia including primary afferent fibers, interneurons in spinal cord, and so forth. 5,6 Although many research works have focused more attention on the establishing procedure of dynamic allodynia, no precise mechanisms and effective therapies documented clearly yet. In our previous studies, we proved that dynamic mechanical hypersensitivity induced by nerve injury or inflammation was compromised in mice with ablation of spinal VT3 Lbx1 neurons, and preserved somatostatin lineage neurons were still largely sufficient to mediate punctate mechanical hypersensitivity.…”

Section: Introductionmentioning

confidence: 99%

Memantine selectively prevented the induction of dynamic allodynia by blocking Kir2.1 channel and inhibiting the activation of microglia in spinal dorsal horn of mice in spared nerve injury model

et al. 2019

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Background Memantine is one of the important clinical medications in treating moderate to severe Alzheimer disease. The effect of memantine on preventing or treating punctate allodynia has been thoroughly studied but not on the induction of dynamic allodynia. The aim of this study is to investigate whether memantine could prevent the induction of dynamic allodynia and its underlying spinal mechanisms. Results (1) In in vivo spared nerve injury pain model, pretreatment with memantine at a lower dose (10 nmol, intrathecal; memantine-10) selectively prevented the induction of dynamic allodynia but not the punctate allodynia. (2) Pretreatment with either MK801-10 (MK801-10 nmol, intrathecal) or higher dose of memantine (30 nmol, intrathecal; memantine-30) prevented the induction of both dynamic and punctate allodynia. (3) Memantine-10 showed significant effect on the inhibition of the spared nerve injury-induced overactivation of microglia in spinal dorsal horn. (4) In contrast, in complete freund′s adjuvant (CFA) model, memantine-10 neither affected the CFA injection-induced activation of microglia in spinal dorsal horn nor the induction of dynamic allodynia. (5) Immunohistological studies showed Kir2.1 channel distributed widely and co-localized with microglia in the spinal dorsal horn of mice. (6) Pretreatment with either minocycline, a microglia inhibitor, or ML133, a Kir2.1 inhibitor, both selectively prevented the overactivation of microglia in spinal dorsal horn and the induction of dynamic allodynia following spared nerve injury. Conclusion The selective inhibitory effect on the induction of dynamic allodynia in spared nerve injury model by low dose of the memantine (memantine-10) was tightly correlated with the blockade of microglia Kir2.1 channel to suppress the microglia activation.

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Peripheral afferents and spinal inhibitory system in dynamic and static mechanical allodynia

Cited by 27 publications

References 59 publications

Prevalence and characteristics of cutaneous allodynia in probable migraine

Prevalence and characteristics of cutaneous allodynia in probable migraine

Low-Dose Interleukin-2 and Regulatory T Cell Treatments Attenuate Punctate and Dynamic Mechanical Allodynia in a Mouse Model of Sciatic Nerve Injury

Memantine selectively prevented the induction of dynamic allodynia by blocking Kir2.1 channel and inhibiting the activation of microglia in spinal dorsal horn of mice in spared nerve injury model

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