Neuronal Sensitization and Synaptic Facilitation in the Superficial Dorsal Horn of a Rat Reserpine-induced Pain Model

Uta, Daisuke; Tsuboshima, Katsuyuki; Nishijo, Hisao; Mizumura, Kazue; Taguchi, Toru

doi:10.1016/j.neuroscience.2021.10.010

Cited by 16 publications

(17 citation statements)

References 43 publications

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“…All these events may contribute to afferent hyperexcitability in the ASI model, with greater neurotransmitter release in the dorsal horn neurons that may contribute to a greater activation of these neurons, as well as to their central sensitization. Although these peripheral mechanisms can be clearly attributable to the ASI model, it is worth mentioning that it has been described also peripheral mechanisms in reserpine model 17 , 21 , 42 . Animals treated with repeated administrations of reserpine may show increased sensitivity of nociceptive afferent fibers to mechanical stimuli mediated by the increase in ASIC3 channels, and also to painful chemical stimuli (formalin).…”

Section: Discussionmentioning

confidence: 98%

Long-lasting reflexive and nonreflexive pain responses in two mouse models of fibromyalgia-like condition

Deulofeu

Homs

Vela³

et al. 2022

Sci Rep

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Nociplastic pain arises from altered nociception despite no clear evidence of tissue or somatosensory system damage, and fibromyalgia syndrome can be highlighted as a prototype of this chronic pain subtype. Currently, there is a lack of effective treatments to alleviate both reflexive and nonreflexive pain responses associated with fibromyalgia condition, and suitable preclinical models are needed to assess new pharmacological strategies. In this context, although in recent years some remarkable animal models have been developed to mimic the main characteristics of human fibromyalgia, most of them show pain responses in the short term. Considering the chronicity of this condition, the present work aimed to develop two mouse models showing long-lasting reflexive and nonreflexive pain responses after several reserpine (RIM) or intramuscular acid saline solution (ASI) injections. To our knowledge, this is the first study showing that RIM6 and ASI mouse models show reflexive and nonreflexive responses up to 5–6 weeks, accompanied by either astro- or microgliosis in the spinal cord as pivotal physiopathology processes related to such condition development. In addition, acute treatment with pregabalin resulted in reflexive pain response alleviation in both the RIM6 and ASI models. Consequently, both may be considered suitable experimental models of fibromyalgia-like condition, especially RIM6.

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Section: Discussionmentioning

confidence: 98%

Long-lasting reflexive and nonreflexive pain responses in two mouse models of fibromyalgia-like condition

Deulofeu

Homs

Vela³

et al. 2022

Sci Rep

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“…Similarly, animals treated with repeated administrations of reserpine showed increased sensitivity of nociceptive afferent fibers, mediated, at least in part, by ASIC3 channels. Peripheral hypersensitivity in RIM animals leads to overactivation and sensitization of dorsal horn neurons in the spinal cord, accompanied by decreased inhibitory inputs as well as the activation of spinal microglial cells [ 43 , 44 , 45 ]. Pregabalin is known to bind to the alpha-2-delta (α 2 δ 1 ) subunit of voltage-gated calcium channels, located at the terminals of the nociceptive afferents in the dorsal horn, causing presynaptic inhibition of calcium influx, and thus reduced calcium-induced release of excitatory neurotransmitters, including glutamate [ 46 ], thereby reducing the excitability of the spinal nociceptive neurons to relieve pain [ 47 ].…”

Section: Resultsmentioning

confidence: 99%

Long-Lasting Nociplastic Pain Modulation by Repeated Administration of Sigma-1 Receptor Antagonist BD1063 in Fibromyalgia-like Mouse Models

Bagó-Mas

Deulofeu

Vela³

et al. 2022

IJMS

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Sigma-1 receptor (s1R) ligands have been shown to be effective at relieving neuropathic and inflammatory pain, but have not yet been tested in experimental models of fibromyalgia. The objective of this study was to evaluate the effect of a s1R antagonist (BD1063) compared to pregabalin. ICR-CD1 female mice were subjected to either six repeated injections of reserpine, to cause reserpine-induced myalgia (RIM6), or acidified saline intramuscular injections (ASI). In these two models, we evaluated the effect of BD1063 and pregabalin on thermal hypersensitivity, anxiety-like and depression-like behaviors, and on spinal cord gliosis. BD1063 exerted an antinociceptive effect on both reflexive (thermal hyperalgesia) and nonreflexive (anxiety- and depression-like) pain behaviors, and reduced spinal astroglial and microglial reactivity, following repeated treatment for 2 weeks. Interestingly, the effects of BD1063 were long-term, lasting several weeks after treatment discontinuation in both fibromyalgia-like models. Similar results were obtained with pregabalin, but the effects on pain behaviors lasted for a shorter length of time, and pregabalin did not significantly modulate spinal glial reactivity. The inhibitory and long-lasting effect of pharmacological blockade of s1Rs on both sensory and affective dimensions of nociplastic-like pain and spinal cord gliosis in two experimental models of fibromyalgia support the application of this therapeutic strategy to treat fibromyalgia.

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“…In previous electrophysiological studies of the spinal cord, pain and itch in peripheral areas, such as the limbs, have been analyzed by in vivo extracellular recording and patch-clamp recording in the lumbar spinal cord (L1–L6), which receives input from the limbs [ 17 , 18 , 19 , 20 , 21 ]. In addition, a method to analyze the characteristics of the brain-spinal cord neuronal pathway by electrophysiological studies in the lumbar spinal cord to investigate the involvement of hormones in ejaculation has been recently reported [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Developing a Novel Method for the Analysis of Spinal Cord–Penile Neurotransmission Mechanisms

Uta

Kiyohara²,

Nagaoka³

et al. 2023

IJMS

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Sexual dysfunction can be caused by impaired neurotransmission from the peripheral to the central nervous system. Therefore, it is important to evaluate the input of sensory information from the peripheral genital area and investigate the control mechanisms in the spinal cord to clarify the pathological basis of sensory abnormalities in the genital area. However, an in vivo evaluation system for the spinal cord–penile neurotransmission mechanism has not yet been developed. Here, urethane-anesthetized rats were used to evaluate neuronal firing induced by innocuous or nociceptive stimulation of the penis using extracellular recording or patch-clamp techniques in the lumbosacral spinal dorsal horn and electrophysiological evaluation in the peripheral pelvic nerves. As a result, innocuous and nociceptive stimuli-evoked neuronal firing was successfully recorded in the deep and superficial spinal dorsal horns, respectively. The innocuous stimuli-evoked nerve firing was also recorded in the pelvic nerve. These firings were suppressed by lidocaine. To the best of our knowledge, this is the first report of a successful quantitative evaluation of penile stimuli-evoked neuronal firing. This method is not only useful for analyzing the pathological basis of spinal cord–penile neurotransmission in sexual dysfunction but also provides a useful evaluation system in the search for new treatments.

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Neuronal Sensitization and Synaptic Facilitation in the Superficial Dorsal Horn of a Rat Reserpine-induced Pain Model

Cited by 16 publications

References 43 publications

Long-lasting reflexive and nonreflexive pain responses in two mouse models of fibromyalgia-like condition

Long-lasting reflexive and nonreflexive pain responses in two mouse models of fibromyalgia-like condition

Long-Lasting Nociplastic Pain Modulation by Repeated Administration of Sigma-1 Receptor Antagonist BD1063 in Fibromyalgia-like Mouse Models

Developing a Novel Method for the Analysis of Spinal Cord–Penile Neurotransmission Mechanisms

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