Injury Induced Activation of Extracellular Signal-Regulated Kinase (ERK) in the Rat Rostral Ventromedial Medulla (RVM) is Age Dependant and Requires the Lamina I Projection Pathway

Géranton, Sandrine M; Tochiki, Keri K; Chiu, Winnie Wy; Stuart, Sarah A; Hunt, Stephen P.

doi:10.1186/1744-8069-6-54

Cited by 16 publications

(11 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The involvement of pERK1/2 in the maintenance of chronic neuropathic pain is well established (Geranton, Tochiki, Chiu, Stuart, & Hunt, ; Ma & Quirion, ; Song et al, ). SNI animals receiving amylin chronically presented a significantly higher number of pERK1/2‐positive cells than both SHAM groups, suggesting amylin may trigger the ERK1/2 cascade under neuropathic conditions.…”

Section: Discussionmentioning

confidence: 99%

Amylin, a peptide expressed by nociceptors, modulates chronic neuropathic pain

Almeida

Castro-Lopes

Neto

et al. 2019

European Journal of Pain

View full text Add to dashboard Cite

Background Amylin is a calcitonin gene‐related peptide family member expressed by nociceptors. Amylin's expression is down‐regulated following nerve damage, and studies suggested it affects nociception. We aimed at clarifying amylin's effects on chronic neuropathic pain and investigating its site of action. Methods Chronic neuropathic pain was induced in rats by spared nerve injury (SNI) surgery. Mechanical allodynia/hyperalgesia and cold allodynia/hyperalgesia were assessed by the von Frey, pinprick, acetone and cold plate behavioural tests, respectively. Amylin, amylin‐receptor antagonist (AC187) or vehicle solutions were delivered chronically, by a subcutaneous (SC) mini‐osmotic pump, or acutely, by SC or intrathecal (IT) injections. Cellular and fibre markers were used to detect spinal cord alterations in SNI rats after chronic amylin administration. Results Continuous subcutaneous amylin administration aggravated cold allodynia in SNI animals, possibly via amylin‐receptors (AmyR) in supraspinal areas. Acute intrathecal administration of amylin attenuated mechanical hyperalgesia, whereas AC187 reduced mechanical allodynia, suggesting distinct roles of endogenous amylin and of pharmacological amylin doses when targeting spinal cord amylin receptors. Chronic amylin administration promoted c‐Fos activation only in the dorsal horn neurons of SHAM animals, suggesting a distinctive role of amylin in the activation of the spinal neuronal circuitry under neuropathic and physiological conditions. ERK1/2 phosphorylation increased in the dorsal horn neurons of SNI rats chronically treated with amylin. This ERK1/2 cascade activation may be related to amylin's effect on the aggravation of cold allodynia in SNI rats. Conclusions Amylin's nociceptive effects seem to depend on the treatment duration and route of administration by acting at different levels of the nervous system. Significance Amylin modulated neuropathic pain by acting at different levels of the nervous system. Whereas supraspinal areas may be involved in amylin's induced pronociception, modulation of spinal cord amylin receptors by endogenous or pharmacological amylin doses triggers both pro‐ and antinociceptive effects.

show abstract

Section: Discussionmentioning

confidence: 99%

Amylin, a peptide expressed by nociceptors, modulates chronic neuropathic pain

Almeida

Castro-Lopes

Neto

et al. 2019

European Journal of Pain

View full text Add to dashboard Cite

show abstract

“…In the brainstem raphe sub‐nuclei, the chronic constriction injury was associated with increased pERK expression. Increased pERK in the raphe magnus is also reported following spared nerve injury, which has been shown very convincingly to contribute to the increased sensitivity to mechanical stimuli and to depend on lamina I and II inputs (Geranton et al., ). The expression of pERK1/2 was selectively decreased in the raphe obscurus by acute noxious stimulation in rats with mononeuropathy, which stood in contrast to their non‐neuropathic counterparts in which it was increased.…”

mentioning

confidence: 92%

pERK‐ing up the brainstem after injury

Keay

2012

European Journal of Pain

View full text Add to dashboard Cite

“…Depletion of the spinal serotonin reduced the activation of the ERK evoked by the formalin. It has also been demonstrated that the ERK is activated in the RVM following peripheral inflammation or injury, and much of the ERK activation has been found in the serotonergic neurons [ 28 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

Expression of the spinal 5-HT7 receptor and p-ERK pathway in the carrageenan inflammatory pain of rats

Cho

Kim

et al. 2015

Korean J Anesthesiol

View full text Add to dashboard Cite

BackgroundAlthough the inhibitory role of the 5-hydroxytrypatmine receptor 7(5-HT7R) on nociceptive processing is generally recognized, an excitatory effect associated with a reduced 5-HT7R expression has also been observed in the nerve injury model. In the carrageenan model, no significant effect is produced by the 5-HT7R activation, but the change in 5-HT7R expression has not been examined. Lesioning of the spinal serotonergic pathway enhances allodynia in the carrageenan model, but it also relieves several other pain states, including in the formalin model. While lesioning suppresses the activation of the extracellular signal-regulated kinase (ERK) of the spinal cord in the formalin model, its role in the carrageenan model has not been reported.MethodsFollowing intraplantar injections of carrageenan, the spinal 5-HT7R expression was examined using Western blotting in male Sprague-Dawley rats. The effect of serotonergic pathway lesioning with intrathecal 5,7-dihydroxytryptamine (5,7-DHT) on the expression of the phospho-ERK was measured.ResultsThe expression of the 5-HT7R in the carrageenan model was not significantly different from that of naive animals. The expression of the spinal p-ERK in the carrageenan model was significantly increased, but returned to the level of a naive rat 1 hour after the carrageenan injection. However, it remained significantly higher 1 hour after the injection in the animals treated with 5,7-DHT than in the naive and control rats.ConclusionsThe expression of the spinal 5-HT7R is not altered by peripheral inflammation with carrageenan, suggesting that the lack of antinociceptive effect of the 5-HT7R activation is partly attributable to the absence of changes in the expression of the 5-HT7R in the spinal cord. The extended increase of the spinal p-ERK might be related to the enhanced pain behavior in the animals with lesions of the spinal serotonergic pathway in the carrageenan model.

show abstract

Injury Induced Activation of Extracellular Signal-Regulated Kinase (ERK) in the Rat Rostral Ventromedial Medulla (RVM) is Age Dependant and Requires the Lamina I Projection Pathway

Cited by 16 publications

References 43 publications

Amylin, a peptide expressed by nociceptors, modulates chronic neuropathic pain

Amylin, a peptide expressed by nociceptors, modulates chronic neuropathic pain

pERK‐ing up the brainstem after injury

Expression of the spinal 5-HT7 receptor and p-ERK pathway in the carrageenan inflammatory pain of rats

Contact Info

Product

Resources

About