Enhanced serotonin and mesolimbic dopamine transmissions in a rat model of neuropathic pain

Claudia Sagheddu, Sonia Aroni, Marta De Felice, Salvatore Lecca, Antonio Luchicchi, Miriam Melis, Anna Lisa Muntoni, Rosaria Romano, Enza Palazzo, Francesca Guida, Sabatino Maione, Marco Pistis

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

In humans, affective consequences of neuropathic pain, ranging from depression to anxiety and anhedonia, severely impair quality of life and are a major disease burden, often requiring specific medications. Depressive- and anxiety-like behaviors have also been observed in animal models of peripheral nerve injury. Dysfunctions in central nervous system monoamine transmission have been hypothesized to underlie depressive and anxiety disorders in neuropathic pain. To assess whether these neurons display early changes in their activity that in the long-term might lead to chronicization, maladaptive plasticity and affective consequences, we carried out in vivo extracellular single unit recordings from serotonin neurons in the dorsal raphe nucleus (DRN) and from dopamine neurons in ventral tegmental area (VTA) in the spared nerve injury (SNI) model of neuropathic pain in rats. Extracellular dopamine levels and the expression of dopamine D1, D2 receptors and tyrosine hydroxylase (TH) were measured in the nucleus accumbens. We report that, two weeks following peripheral nerve injury, discharge rate of serotonin DRN neurons and burst firing of VTA dopamine cells are enhanced, when compared with sham-operated animals. We also observed higher extracellular dopamine levels and reduced expression of D2, but not D1, receptors and TH in the nucleus accumbens. Our study confirms that peripheral neuropathy induces changes in the serotonin and dopamine systems that might be the early result of chronic maladaptation to persistent pain. The allostatic activation of these neural systems, which mirrors that already described as a consequence of stress, might lead to depression and anxiety previously observed in neuropathic animals but also an attempt to cope positively with the negative experience.

Original languageEnglish
Pages (from-to)383-93
Number of pages11
JournalNeuropharmacology
Volume97
DOIs
Publication statusPublished - Oct 2015
Externally publishedYes

Cite this

Sagheddu, Claudia ; Aroni, Sonia ; De Felice, Marta ; Lecca, Salvatore ; Luchicchi, Antonio ; Melis, Miriam ; Muntoni, Anna Lisa ; Romano, Rosaria ; Palazzo, Enza ; Guida, Francesca ; Maione, Sabatino ; Pistis, Marco. / Enhanced serotonin and mesolimbic dopamine transmissions in a rat model of neuropathic pain. In: Neuropharmacology. 2015 ; Vol. 97. pp. 383-93.
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title = "Enhanced serotonin and mesolimbic dopamine transmissions in a rat model of neuropathic pain",
abstract = "In humans, affective consequences of neuropathic pain, ranging from depression to anxiety and anhedonia, severely impair quality of life and are a major disease burden, often requiring specific medications. Depressive- and anxiety-like behaviors have also been observed in animal models of peripheral nerve injury. Dysfunctions in central nervous system monoamine transmission have been hypothesized to underlie depressive and anxiety disorders in neuropathic pain. To assess whether these neurons display early changes in their activity that in the long-term might lead to chronicization, maladaptive plasticity and affective consequences, we carried out in vivo extracellular single unit recordings from serotonin neurons in the dorsal raphe nucleus (DRN) and from dopamine neurons in ventral tegmental area (VTA) in the spared nerve injury (SNI) model of neuropathic pain in rats. Extracellular dopamine levels and the expression of dopamine D1, D2 receptors and tyrosine hydroxylase (TH) were measured in the nucleus accumbens. We report that, two weeks following peripheral nerve injury, discharge rate of serotonin DRN neurons and burst firing of VTA dopamine cells are enhanced, when compared with sham-operated animals. We also observed higher extracellular dopamine levels and reduced expression of D2, but not D1, receptors and TH in the nucleus accumbens. Our study confirms that peripheral neuropathy induces changes in the serotonin and dopamine systems that might be the early result of chronic maladaptation to persistent pain. The allostatic activation of these neural systems, which mirrors that already described as a consequence of stress, might lead to depression and anxiety previously observed in neuropathic animals but also an attempt to cope positively with the negative experience.",
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author = "Claudia Sagheddu and Sonia Aroni and {De Felice}, Marta and Salvatore Lecca and Antonio Luchicchi and Miriam Melis and Muntoni, {Anna Lisa} and Rosaria Romano and Enza Palazzo and Francesca Guida and Sabatino Maione and Marco Pistis",
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Sagheddu, C, Aroni, S, De Felice, M, Lecca, S, Luchicchi, A, Melis, M, Muntoni, AL, Romano, R, Palazzo, E, Guida, F, Maione, S & Pistis, M 2015, 'Enhanced serotonin and mesolimbic dopamine transmissions in a rat model of neuropathic pain' Neuropharmacology, vol. 97, pp. 383-93. https://doi.org/10.1016/j.neuropharm.2015.06.003

Enhanced serotonin and mesolimbic dopamine transmissions in a rat model of neuropathic pain. / Sagheddu, Claudia; Aroni, Sonia; De Felice, Marta; Lecca, Salvatore; Luchicchi, Antonio; Melis, Miriam; Muntoni, Anna Lisa; Romano, Rosaria; Palazzo, Enza; Guida, Francesca; Maione, Sabatino; Pistis, Marco.

In: Neuropharmacology, Vol. 97, 10.2015, p. 383-93.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Enhanced serotonin and mesolimbic dopamine transmissions in a rat model of neuropathic pain

AU - Sagheddu, Claudia

AU - Aroni, Sonia

AU - De Felice, Marta

AU - Lecca, Salvatore

AU - Luchicchi, Antonio

AU - Melis, Miriam

AU - Muntoni, Anna Lisa

AU - Romano, Rosaria

AU - Palazzo, Enza

AU - Guida, Francesca

AU - Maione, Sabatino

AU - Pistis, Marco

N1 - Copyright © 2015 Elsevier Ltd. All rights reserved.

PY - 2015/10

Y1 - 2015/10

N2 - In humans, affective consequences of neuropathic pain, ranging from depression to anxiety and anhedonia, severely impair quality of life and are a major disease burden, often requiring specific medications. Depressive- and anxiety-like behaviors have also been observed in animal models of peripheral nerve injury. Dysfunctions in central nervous system monoamine transmission have been hypothesized to underlie depressive and anxiety disorders in neuropathic pain. To assess whether these neurons display early changes in their activity that in the long-term might lead to chronicization, maladaptive plasticity and affective consequences, we carried out in vivo extracellular single unit recordings from serotonin neurons in the dorsal raphe nucleus (DRN) and from dopamine neurons in ventral tegmental area (VTA) in the spared nerve injury (SNI) model of neuropathic pain in rats. Extracellular dopamine levels and the expression of dopamine D1, D2 receptors and tyrosine hydroxylase (TH) were measured in the nucleus accumbens. We report that, two weeks following peripheral nerve injury, discharge rate of serotonin DRN neurons and burst firing of VTA dopamine cells are enhanced, when compared with sham-operated animals. We also observed higher extracellular dopamine levels and reduced expression of D2, but not D1, receptors and TH in the nucleus accumbens. Our study confirms that peripheral neuropathy induces changes in the serotonin and dopamine systems that might be the early result of chronic maladaptation to persistent pain. The allostatic activation of these neural systems, which mirrors that already described as a consequence of stress, might lead to depression and anxiety previously observed in neuropathic animals but also an attempt to cope positively with the negative experience.

AB - In humans, affective consequences of neuropathic pain, ranging from depression to anxiety and anhedonia, severely impair quality of life and are a major disease burden, often requiring specific medications. Depressive- and anxiety-like behaviors have also been observed in animal models of peripheral nerve injury. Dysfunctions in central nervous system monoamine transmission have been hypothesized to underlie depressive and anxiety disorders in neuropathic pain. To assess whether these neurons display early changes in their activity that in the long-term might lead to chronicization, maladaptive plasticity and affective consequences, we carried out in vivo extracellular single unit recordings from serotonin neurons in the dorsal raphe nucleus (DRN) and from dopamine neurons in ventral tegmental area (VTA) in the spared nerve injury (SNI) model of neuropathic pain in rats. Extracellular dopamine levels and the expression of dopamine D1, D2 receptors and tyrosine hydroxylase (TH) were measured in the nucleus accumbens. We report that, two weeks following peripheral nerve injury, discharge rate of serotonin DRN neurons and burst firing of VTA dopamine cells are enhanced, when compared with sham-operated animals. We also observed higher extracellular dopamine levels and reduced expression of D2, but not D1, receptors and TH in the nucleus accumbens. Our study confirms that peripheral neuropathy induces changes in the serotonin and dopamine systems that might be the early result of chronic maladaptation to persistent pain. The allostatic activation of these neural systems, which mirrors that already described as a consequence of stress, might lead to depression and anxiety previously observed in neuropathic animals but also an attempt to cope positively with the negative experience.

KW - Action Potentials

KW - Animals

KW - Disease Models, Animal

KW - Dopamine

KW - Dopaminergic Neurons

KW - Dorsal Raphe Nucleus

KW - Hyperalgesia

KW - Male

KW - Neuralgia

KW - Nucleus Accumbens

KW - Pain Threshold

KW - Rats, Sprague-Dawley

KW - Receptors, Dopamine D1

KW - Receptors, Dopamine D2

KW - Serotonergic Neurons

KW - Serotonin

KW - Touch

KW - Tyrosine 3-Monooxygenase

KW - Ventral Tegmental Area

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.neuropharm.2015.06.003

DO - 10.1016/j.neuropharm.2015.06.003

M3 - Article

VL - 97

SP - 383

EP - 393

JO - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

ER -