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.
authors.affiliation: Division of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Sagheddu
authors.affiliation: Division of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Aroni
authors.affiliation: Division of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: De Felice
authors.affiliation: Division of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Lecca
authors.affiliation: Division of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Luchicchi
authors.affiliation: Division of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy.
authors.forename: Miriam
authors.initials: M
authors.lastname: Melis
authors.affiliation: Neuroscience Institute, National Research Council of Italy, Section of Cagliari, Italy.
authors.forename: Anna Lisa
authors.initials: AL
authors.lastname: Muntoni
authors.affiliation: Department of Experimental Medicine, Division of Pharmacology, The Second University of Naples, 80138 Naples, Italy.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Romano
authors.affiliation: Department of Experimental Medicine, Division of Pharmacology, The Second University of Naples, 80138 Naples, Italy; Department of Anaesthesiology, Surgery and Emergency, The Second University of Naples, 80138 Naples, Italy.
authors.forename: Enza
authors.initials: E
authors.lastname: Palazzo
authors.affiliation: Department of Experimental Medicine, Division of Pharmacology, The Second University of Naples, 80138 Naples, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Guida
authors.affiliation: Department of Experimental Medicine, Division of Pharmacology, The Second University of Naples, 80138 Naples, Italy.
authors.forename: Sabatino
authors.initials: S
authors.lastname: Maione
authors.affiliation: Division of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy; Neuroscience Institute, National Research Council of Italy, Section of Cagliari, Italy. Electronic address: mpistis@unica.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Pistis
mesh_terms: D000200:Action Potentials; D000818:Animals; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000502:physiology*; D065847:Dorsal Raphe Nucleus / Q000503:physiopathology*; D006930:Hyperalgesia / Q000503:physiopathology; D008297:Male; D009437:Neuralgia / Q000503:physiopathology*; D009714:Nucleus Accumbens / Q000503:physiopathology*; D017288:Pain Threshold / Q000502:physiology; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D059326:Serotonergic Neurons / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism; D014110:Touch; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000503:physiopathology*
chemical_list: D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012701:Serotonin; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine
keywords: Allodynia; Dopamine neurons; Dopamine receptors; Electrophysiology; Neuropathic pain; Rostromedial tegmental nucleus; Serotonin neurons; Spared nerve injury