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

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

doi:10.1016/j.neuropharm.2015.06.003

Cited by 71 publications

(56 citation statements)

References 87 publications

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“…We found that CCI-induced chronic neuropathic pain increased tonic activity and burst firing in contralateral VTA DA neurons and that pharmacological inhibition of this activity attenuated established thermal hyperalgesia. These findings suggest that VTA DA neuron activation plays an important role in mediating chronic pain and are consistent with those from a recent study using another widely used animal model of neuropathic pain, mice with spared nerve injury (14). In vivo electrophysiological recordings from those mice revealed an increase in phasic firing activity in the contralateral VTA DA neurons and enhanced DA release in the NAc.…”

Section: Discussionsupporting

confidence: 91%

Brain-Derived Neurotrophic Factor in the Mesolimbic Reward Circuitry Mediates Nociception in Chronic Neuropathic Pain

Zhang

Qian

et al. 2017

Biological Psychiatry

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BACKGROUND The mesolimbic reward system plays a critical role in modulating nociception; however, its underlying molecular, cellular, and neural circuitry mechanisms remain unknown. METHODS Chronic constrictive injury (CCI) of the sciatic nerve was used to model neuropathic pain. Projection-specific in vitro recordings in mouse brain slices and in vivo recordings from anesthetized animals were used to measure firing of dopaminergic (DA) neurons in the ventral tegmental area (VTA). The role of VTA–nucleus accumbens (NAc) circuitry in nociceptive regulation was assessed using optogenetic and pharmacological manipulations, and the underlying molecular mechanisms were investigated by Western blotting, enzyme-linked immunosorbent assays, and conditional knockdown techniques. RESULTS c-Fos expression in and firing of contralateral VTA–NAc DA neurons were elevated in CCI mice, and optogenetic inhibition of these neurons reversed CCI-induced thermal hyperalgesia. CCI increased the expression of brain-derived neurotrophic factor (BDNF) protein but not mRNA in the contralateral NAc. This increase was reversed by pharmacological inhibition of VTA DA neuron activity, which induced an antinociceptive effect that was neutralized by injecting exogenous BDNF into the NAc. Moreover, inhibition of BDNF synthesis in the VTA with anisomycin or selective knockdown of BDNF in the VTA–NAc pathway were antinociceptive in CCI mice. CONCLUSIONS These results reveal a novel mechanism of nociceptive modulation in the mesolimbic reward circuitry and provide new insight into the neural circuits involved in the processing of nociceptive information.

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Section: Discussionsupporting

confidence: 91%

Brain-Derived Neurotrophic Factor in the Mesolimbic Reward Circuitry Mediates Nociception in Chronic Neuropathic Pain

Zhang

Qian

et al. 2017

Biological Psychiatry

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“…Studies indicate that dopamine has a role in pain processing, especially in the transition from acute to chronic pain. 12,34,57,67 Other studies have shown that drugs that alter dopamine levels in the CNS have beneficial effects on pain. 15,27 Because PLZ and N 2 -AcPLZ both act by inhibiting the MAO enzyme, they both increase dopamine levels in the CNS.…”

Section: Discussionmentioning

confidence: 99%

Manipulation of Neurotransmitter Levels Has Differential Effects on Formalin-Evoked Nociceptive Behavior in Male and Female Mice

Mifflin

Benson

Thorburn

et al. 2016

The Journal of Pain

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“…Very few studies have examined the impact of chronic pain-induced depression in brain reward circuit plasticity. Recent studies using animal models of neuropathic pain link changes in dopamine receptor signal transduction, the amount of released dopamine and other neurochemical adaptations in the midbrain dopamine circuit with depression-like behaviors and reduced motivation (Ozaki et al, 2002, 2004, Terzi et al, 2014, Schwartz et al, 2014, Xie et al 2014, Sagheddu, et al, 2015). …”

Section: The Impact Of Chronic Pain On Mood and Motivationmentioning

confidence: 99%

Modulation of pain, nociception, and analgesia by the brain reward center

2016

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The midbrain dopamine center comprises a key network for reward, salience, motivation, and mood. Evidence from various clinical and preclinical settings points to the midbrain dopamine circuit as an important modulator of pain perception and pain-induced anxiety and depression. This review summarizes recent findings that shed light to the neuroanatomical, electrophysiological and molecular adaptations that chronic pain conditions promote in the mesolimbic dopamine system. Chronic pain states induce changes in neuronal plasticity and functional connectivity in several parts of the brain reward center, including nucleus accumbens, the ventral tegmental area and the prefrontal cortex. Here, we discuss recent findings on the mechanisms involved in the perception of chronic pain, in pain-induced anxiety and depression, as well as in pain-killer addiction vulnerability. Several new studies also show that the mesolimbic dopamine circuit potently modulates responsiveness to opioids and antidepressants used for the treatment of chronic pain. We discuss recent data supporting a role of the brain reward pathway in treatment efficacy and we summarize novel findings on intracellular adaptations in the brain reward circuit under chronic pain states.

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

Cited by 71 publications

References 87 publications

Brain-Derived Neurotrophic Factor in the Mesolimbic Reward Circuitry Mediates Nociception in Chronic Neuropathic Pain

Brain-Derived Neurotrophic Factor in the Mesolimbic Reward Circuitry Mediates Nociception in Chronic Neuropathic Pain

Manipulation of Neurotransmitter Levels Has Differential Effects on Formalin-Evoked Nociceptive Behavior in Male and Female Mice

Modulation of pain, nociception, and analgesia by the brain reward center

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