Chapter 13 Descending inhibitory systems

Pertovaara, Antti; Almeida, Armando

doi:10.1016/s0072-9752(06)80017-5

Cited by 70 publications

(60 citation statements)

References 168 publications

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“…Accordingly, this study showed activations in the ipsilateral DLPT during painful mechanical stimulation prior to sensitization. Moreover these activations correlated with activations in ipsilateral dGM, possibly reflecting either an augmented activation of endogenous inhibition by higher activation of projection neurons [7] or a noradrenergic activation of spinal ININs (indirect inhibition of projection neurons) as it has been shown in animal studies [35]. Similarly, previous fMRI studies also showed activations of the DLPT during painful stimuli in healthy humans [15], [36].…”

Section: Discussionsupporting

confidence: 70%

Spinal fMRI Reveals Decreased Descending Inhibition during Secondary Mechanical Hyperalgesia

Rempe

Wolff²,

Riedel³

et al. 2014

PLoS ONE

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Mechanical hyperalgesia is one distressing symptom of neuropathic pain which is explained by central sensitization of the nociceptive system. This sensitization can be induced experimentally with the heat/capsaicin sensitization model. The aim was to investigate and compare spinal and supraspinal activation patterns of identical mechanical stimulation before and after sensitization using functional spinal magnetic resonance imaging (spinal fMRI). Sixteen healthy subjects (6 female, 10 male, mean age 27.2±4.0 years) were investigated with mechanical stimulation of the C6 dermatome of the right forearm during spinal fMRI. Testing was always performed in the area outside of capsaicin application (i.e. area of secondary mechanical hyperalgesia). During slightly noxious mechanical stimulation before sensitization, activity was observed in ipsilateral dorsolateral pontine tegmentum (DLPT) which correlated with activity in ipsilateral spinal cord dorsal gray matter (dGM) suggesting activation of descending nociceptive inhibition. During secondary mechanical hyperalgesia, decreased activity was observed in bilateral DLPT, ipsilateral/midline rostral ventromedial medulla (RVM), and contralateral subnucleus reticularis dorsalis, which correlated with activity in ipsilateral dGM. Comparison of voxel-based activation patterns during mechanical stimulation before/after sensitization showed deactivations in RVM and activations in superficial ipsilateral dGM. This study revealed increased spinal activity and decreased activity in supraspinal centers involved in pain modulation (SRD, RVM, DLPT) during secondary mechanical hyperalgesia suggesting facilitation of nociception via decreased endogenous inhibition. Results should help prioritize approaches for further in vivo studies on pain processing and modulation in humans.

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Section: Discussionsupporting

confidence: 70%

Spinal fMRI Reveals Decreased Descending Inhibition during Secondary Mechanical Hyperalgesia

Rempe

Wolff²,

Riedel³

et al. 2014

PLoS ONE

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“…However, the finding that the TRPC4/C5 antagonist failed to influence pain behavior of neuropathic animals when microinjected into a control site, the internal capsule, supports the interpretation that the TRPC4/C5 antagonist-induced suppression of neuropathic pain behavior in the present study was due to action on the amygdala rather than elsewhere in the brain. In line with this, it has been shown that TRPC4/C5 in the amygdala are expressed particularly in the lateral nucleus [17,18], which has direct and indirect intra-amygdaloid projections to the CeA [10], the main sensory output nucleus that is involved in processing of pain-related signals and that through its connections to the brainstem can contribute to the descending control of pain [14,16].…”

mentioning

confidence: 75%

“…Amygdala, particularly its lateral capsular subdivision within the central nucleus (CeA), the main output pathway to the brainstem, is also involved in processing and regulation of emotional aspects of pain and, through its efferent brainstem projections, in descending control of spinal pain-relay neurons [14,16]. Recently, it was demonstrated that among multiple amygdaloid mechanisms involved in the control of anxiety-driven behaviors are transient potential channels 4 and 5 (TRPC4/C5) that are members of the TRPC1/4/5 subfamily and that gate afferent amygdaloid inputs in the lateral nucleus of the amygdala [17,18].…”

Section: Introductionmentioning

confidence: 99%

“…It may be hypothesized that TRPC4/C5-expressing amygdaloid neurons through projections to the CeA may regulate amygdaloid processing of nociception and thereby also amygdaloid outputs to brainstem pain regulation centers. Since the amygdala is involved both in pain and affect and has reciprocal connections with the pain system [14,16], it may be speculated that amygdala in general and amygdaloid TRPC4/C5 in particular might be among neural substrates contributing to the comorbidity between affect, such as anxiety, and chronic pain (see for refs. e.g., [2]).…”

Section: Introductionmentioning

confidence: 99%

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Regulation of neuropathic pain behavior by amygdaloid TRPC4/C5 channels

Wang

Sagalajev

Yüzer

et al. 2015

Neuroscience Letters

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Pain per se may increase anxiety and conversely, anxiety may increase pain. Therefore, a positive feedback loop between anxiety and pain possibly contributes to pain and suffering in some pathophysiological pain conditions, such as that induced by peripheral nerve injury. Recent results indicate that transient receptor channels 4 and 5 (TRPC4/C5) in the amygdala have anxiogenic effects in rodents, while their role in chronic pain conditions is not known. Here, we studied whether the amygdaloid TRPC4/C5 that are known to have anxiogenic properties contribute to the maintenance of sensory or affective aspects of pain in an experimental model of peripheral neuropathy. Rats with a spared nerve injury (SNI) model of neuropathy in the left hind limb had a chronic cannula for microinjections of drugs into the right amygdala or the internal capsule (a control site). Sensory pain was assessed by determining mechanical hypersensitivity with calibrated monofilaments and affective pain by determining aversive place-conditioning. Amygdaloid treatment with ML-204, a TRPC4/C5 antagonist, produced a dose-related (5-10 μg) antihypersensitivity effect, without obvious side-effects. Additionally, amygdaloid administration of ML-204 reduced affective-like pain behavior. In the internal capsule, ML-204 had no effect on hypersensitivity or affective-like pain in SNI animals. In healthy controls, amygdaloid administration of ML-204 failed to influence pain behavior induced by mechanical stimulation or noxious heat. The results indicate that the amygdaloid TRPC4/C5 contribute to maintenance of pain hypersensitivity and pain affect in neuropathy.

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“…Although most of these mechanisms exert broad bilateral pain-inhibitory effects (Pertovaara and Almeida 2006), noradrenergic pathways inhibit nociceptive activity hemilaterally (Tsuruoka and Willis 1996a, b;Tsuruoka et al 1999;Tsuruoka et al 2003) via projections from the locus coeruleus that act on spinal α 2 -adrenoreceptors (Clark and Proudfit 1992;Jones and Gebhart 1986b, a). Interestingly, in rats with bilateral lesions of the locus coeruleus, paw withdrawal latencies were found to be shorter not only in the carrageenan-inflamed hindpaw but also in the ipsilateral non-inflamed forepaw (Tsuruoka et al 2004).…”

Section: Analgesia To Blunt Pressure In the Foreheadmentioning

confidence: 99%