Amylin modulates the formalin‐induced tonic pain behaviours in rats

Potes, Catarina Soares; Pestana, Ana; Pontes, Mariana Chiste; Caramelo, Ana; Neto, Francisco Piorino

doi:10.1002/ejp.898

Cited by 9 publications

(14 citation statements)

References 53 publications

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“…However, subcutaneously delivered amylin may cross the BBB (Banks & Kastin, ; Banks et al, ) and act at supraspinal levels having amylin binding sites and CTR expression (Becskei et al, ; van Rossum et al, ). Brain areas involved in the cognitive‐affective component of pain and/or belonging to the descending pain modulatory pathways (Maeda, Tsuruoka, Hayashi, Nagasawa, & Inoue, ; Neugebauer, Li, Bird, & Han, ) are activated by subcutaneous amylin and may play a role in amylin‐mediated nociceptive effects (Potes et al, ; Rowland, Crews, & Gentry, ). Here, a transient antinociceptive effect was detected, with attenuation of mechanical hyperalgesia 30 min after intrathecal amylin injection into the spinal segments receiving innervation from the hindpaw.…”

Section: Discussionmentioning

confidence: 99%

“…The selected amylin doses (100 µg/Kg and 0.5 µg/µl for acute subcutaneous and intrathecal administrations, respectively; 2 µg Kg -1 hr -1 for chronic SC administration), volumes and time of administration were based on studies in rats and mice regarding the nociceptive and anti-inflammatory amylin actions (Bouali et al, 1995;Clementi et al, 1995;Huang et al, 2010;Potes et al, 2016;Sibilia et al, 2000;Young, 1997), on transient and sustained anorectic amylin effects after acute and chronic administrations (Lutz, Mollet, Rushing, Riediger, & Scharrer, 2001;Lutz et al, 1998;Potes & Lutz, 2010), and on own preliminary data. AC187, derived from salmon calcitonin, acts as a selective competitive antagonist of amylin receptors (Howitt & Poyner, 1997;Young et al, 1994).…”

Section: Drugsmentioning

confidence: 99%

“…AC187, derived from salmon calcitonin, acts as a selective competitive antagonist of amylin receptors (Howitt & Poyner, 1997;Young et al, 1994). The selected dose (3 μg/ μl) used for acute IT administration was based on previous studies (Grabler & Lutz, 2004;Lutz, Tschudy, Rushing, & Scharrer, 2000;Mollet, Gilg, Riediger, & Lutz, 2004;Potes et al, 2016;Reidelberger et al, 2004;Rushing et al, 2001).…”

Section: Drugsmentioning

confidence: 99%

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

Almeida

Castro-Lopes

Neto

et al. 2019

European Journal of Pain

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Drugsmentioning

confidence: 99%

Section: Drugsmentioning

confidence: 99%

See 1 more Smart Citation

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

Almeida

Castro-Lopes

Neto

et al. 2019

European Journal of Pain

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“…As noted, both CGRP and amylin are reported to have effects relating to pain, though there are still limited data and it is unclear how much overlap there is because the peptides are not usually tested in the same study . Amylin reduces pain in formalin and acetic acid tests, it has analgesic effects in models of visceral pain when administered peripherally, and antinociceptive effects are linked to reduced spinal c‐fos expression; on the other hand, no effects were evident in a tail‐immersion test when given centrally . However, amylin knockout mice have reduced nociception .…”

Section: Amylin: Pain and Other Actionsmentioning

confidence: 99%

“…56 Amylin reduces pain in formalin and acetic acid tests, it has analgesic effects in models of visceral pain when administered peripherally, and antinociceptive effects are linked to reduced spinal c-fos expression; on the other hand, no effects were evident in a tail-immersion test when given centrally. [57][58][59][60][61] However, amylin knockout mice have reduced nociception. 62 In all cases, there is no clear evidence that a particular amylin receptor is involved, given the complexity in the amylin receptor system.…”

Section: Amylin: Pain and Other Actionsmentioning

confidence: 99%

Amylin

Hay

2017

Headache

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Amylin is a 37 amino acid peptide hormone that is closely related to calcitonin gene-related peptide (CGRP). Amylin and CGRP share a receptor and are reported to have several similar biological actions. Given the important role of CGRP in migraine and intense efforts to develop drugs against this target, it is important to consider potential areas of overlap between the amylin and CGRP systems. This short review provides a brief introduction to amylin biology, the use of an amylin analog to treat diabetes, and consideration of whether amylin could have any role in headache disorders. Finally, this review informs readers about the AMY 1 (amylin subtype 1) receptor, which is a dual receptor for amylin and CGRP and potentially plays a role in the bioactivity of both of these peptides.

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Amylin Analog Pramlintide Induces Migraine‐like Attacks in Patients

Ghanizada

Al‐Karagholi

Walker

et al. 2021

Annals of Neurology

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Objective Migraine is a prevalent and disabling neurological disease. Its genesis is poorly understood, and there remains unmet clinical need. We aimed to identify mechanisms and thus novel therapeutic targets for migraine using human models of migraine and translational models in animals, with emphasis on amylin, a close relative of calcitonin gene‐related peptide (CGRP). Methods Thirty‐six migraine without aura patients were enrolled in a randomized, double‐blind, 2‐way, crossover, positive‐controlled clinical trial study to receive infusion of an amylin analogue pramlintide or human αCGRP on 2 different experimental days. Furthermore, translational studies in cells and mouse models, and rat, mouse and human tissue samples were conducted. Results Thirty patients (88%) developed headache after pramlintide infusion, compared to 33 (97%) after CGRP (p = 0.375). Fourteen patients (41%) developed migraine‐like attacks after pramlintide infusion, compared to 19 patients (56%) after CGRP (p = 0.180). The pramlintide‐induced migraine‐like attacks had similar clinical characteristics to those induced by CGRP. There were differences between treatments in vascular parameters. Human receptor pharmacology studies showed that an amylin receptor likely mediates these pramlintide‐provoked effects, rather than the canonical CGRP receptor. Supporting this, preclinical experiments investigating symptoms associated with migraine showed that amylin treatment, like CGRP, caused cutaneous hypersensitivity and light aversion in mice. Interpretation Our findings propose amylin receptor agonism as a novel contributor to migraine pathogenesis. Greater therapeutic gains could therefore be made for migraine patients through dual amylin and CGRP receptor antagonism, rather than selectively targeting the canonical CGRP receptor. ANN NEUROL 2021;89:1157–1171

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Amylin modulates the formalin‐induced tonic pain behaviours in rats

Cited by 9 publications

References 53 publications

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

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

Amylin

Amylin Analog Pramlintide Induces Migraine‐like Attacks in Patients

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