Attenuation of hyperalgesia responses via the modulation of 5-hydroxytryptamine signalings in the rostral ventromedial medulla and spinal cord in a 6-hydroxydopamine-induced rat model of Parkinson’s disease

Wang, Chentao; Mao, Cheng‐Jie; Zhang, Xiaoqi; Zhang, Cai-Yi; Lv, Dong-Jun; Yang, Yaping; Xia, Kai-Lin; Liu, Junyi; Wang, Fen; Hu, Lifang; Xu, Guang–Yin; Liu, Chunfeng

doi:10.1177/1744806917691525

Cited by 33 publications

(24 citation statements)

References 58 publications

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“…Compared with sEPSCs, sIPSCs presented a lower frequency of 4.4 ± 0.4 Hz. However, the amplitude of sEPSCs did not differ from that of sIPSCs (10 ± 1.2 pA) (Wang et al, 2017 ). These results differed from those reported by Chong, who recorded all SG neurons from a young adult rat.…”

Section: Discussionmentioning

confidence: 99%

Electrophysiological Properties of Substantia Gelatinosa Neurons in the Preparation of a Slice of Middle-Aged Rat Spinal Cord

et al. 2021

Front. Aging Neurosci.

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A patch-clamp recording in slices generated from the brain or the spinal cord has facilitated the exploration of neuronal circuits and the molecular mechanisms underlying neurological disorders. However, the rodents that are used to generate the spinal cord slices in previous studies involving a patch-clamp recording have been limited to those in the juvenile or adolescent stage. Here, we applied an N-methyl-D-glucamine HCl (NMDG-HCl) solution that enabled the patch-clamp recordings to be performed on the superficial dorsal horn neurons in the slices derived from middle-aged rats. The success rate of stable recordings from substantia gelatinosa (SG) neurons was 34.6% (90/260). When stimulated with long current pulses, 43.3% (39/90) of the neurons presented a tonic-firing pattern, which was considered to represent γ-aminobutyric acid-ergic (GABAergic) signals. Presumptive glutamatergic neurons presented 38.9% (35/90) delayed and 8.3% (7/90) single-spike patterns. The intrinsic membrane properties of both the neuron types were similar but delayed (glutamatergic) neurons appeared to be more excitable as indicated by the decreased latency and rheobase values of the action potential compared with those of tonic (GABAergic) neurons. Furthermore, the glutamatergic neurons were integrated, which receive more excitatory synaptic transmission. We demonstrated that the NMDG-HCl cutting solution could be used to prepare the spinal cord slices of middle-aged rodents for the patch-clamp recording. In combination with other techniques, this preparation method might permit the further study of the functions of the spinal cord in the pathological processes that occur in aging-associated diseases.

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Section: Discussionmentioning

confidence: 99%

Electrophysiological Properties of Substantia Gelatinosa Neurons in the Preparation of a Slice of Middle-Aged Rat Spinal Cord

et al. 2021

Front. Aging Neurosci.

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“…The reduced mechanical and thermal thresholds were acutely attenuated by intra-RVM administration of citalopram to boost 5-HT levels, further implicating serotonergic system dysfunction in these sensory changes. However, conversely, lesioning of serotonergic neurons in the RVM of 6-OHDA rats caused a partial reversal of nociceptive hypersensitivity, 77 implying elevated, rather than reduced, 5-HT transmission in the RVM was behind the sensory changes. This latter finding marries closely with the notion of 5-HT signalling from the RVM facilitating pain transmission in the descending pathways during the development of persistent pain 78 and highlights the need for further investigation into the role of 5-HT in nociceptive hypersensitivity.…”

Section: -Ohdamentioning

confidence: 91%

“…68,76 Serotonergic involvement in the nociceptive hypersensitivity is also implicated. For example, 6-OHDA lesioned rats with nociceptive hypersensitivity show reduced numbers of 5-HT neurons in the rostral ventromedial medulla (RVM) and in the dorsal horn of the spinal cord, 77 suggestive of reduced 5-HT transmission in these pain related regions. The reduced mechanical and thermal thresholds were acutely attenuated by intra-RVM administration of citalopram to boost 5-HT levels, further implicating serotonergic system dysfunction in these sensory changes.…”

Section: -Ohdamentioning

confidence: 99%

Potential of animal models for advancing the understanding and treatment of pain in Parkinson’s disease

Buhidma

Rukavina

Chaudhuri

et al. 2020

npj Parkinsons Dis.

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Pain is a commonly occurring non-motor symptom of Parkinson's disease (PD). Treatment of pain in PD remains less than optimal and a better understanding of the underlying mechanisms would facilitate discovery of improved analgesics. Animal models of PD have already proven helpful for furthering the understanding and treatment of motor symptoms of PD, but could these models offer insight into pain in PD? This review addresses the current position regarding pain in preclinical models of PD, covering the face and predictive validity of existing models and their use so far in advancing understanding of the mechanisms contributing to pain in PD. While pain itself is not usually measured in animals, nociception in the form of thermal, mechanical or chemical nociceptive thresholds offers a useful readout, given reduced nociceptive thresholds are commonly seen in PD patients. Animal models of PD including the reserpine-treated rat and neurodegenerative models such as the MPTP-treated mouse and 6hydroxydopamine (6-OHDA)-treated rat each exhibit reduced nociceptive thresholds, supporting face validity of these models. Furthermore, some interventions known clinically to relieve pain in PD, such as dopaminergic therapies and deep brain stimulation of the subthalamic nucleus, restore nociceptive thresholds in one or more models, supporting their predictive validity. Mechanistic insight gained already includes involvement of central and spinal dopamine and opioid systems. Moving forward, these preclinical models should advance understanding of the cellular and molecular mechanisms underlying pain in PD and provide test beds for examining the efficacy of novel analgesics to better treat this debilitating non-motor symptom.

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“…The analysis was performed in triplicate, and data are expressed as the mean ± standard deviation of three measurements. 25 …”

Section: Methodsmentioning

confidence: 99%

<p>Selective Ablation of Descending Serotonin from the Rostral Ventromedial Medulla Unmasks Its Pro-Nociceptive Role in Chemotherapy-Induced Painful Neuropathy</p>

Liu¹,

Wang²,

Ai³

et al. 2020

JPR

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Purpose: Chemotherapy-induced painful neuropathy (CIPN) is a severe adverse effect of many anti-neoplastic drugs that is difficult to manage. Serotonin (5-hydroxytryptamine, 5-HT) is an important neurotransmitter in the rostral ventromedial medulla (RVM), which modulates descending spinal nociceptive transmission. However, the influence of the descending 5-HT from the RVM on CIPN is poorly understood. We investigated the role of 5-HT released from descending RVM neurons in a paclitaxel-induced CIPN rat model. Methods: CIPN rat model was produced by intraperitoneally injecting of paclitaxel. Pain behavioral assessments included mechanical allodynia and heat hyperalgesia. 5-HT content was analyzed by high-performance liquid chromatography (HPLC). Western blot and immunohistochemistry were used to determine tryptophan hydroxylase (Tph) and c-Fos expression. The inhibitors p-chlorophenylalanine (PCPA) and SB203580 were administrated by stereotaxical RVM microinjection. Ondansetron was injected through intrathecal catheterization. Results: The results demonstrated that Tph, the rate-limiting enzyme in 5-HT synthesis, was significantly upregulated in the RVM, and that spinal 5-HT release was increased in CIPN rats. Intra-RVM microinjection of Tph inhibitor PCPA significantly attenuated mechanical and thermal pain behavior through Tph downregulation and decreased spinal 5-HT. Intra-RVM administration of p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB203580 alleviated paclitaxel-induced pain in a similar manner to PCPA. Intrathecal injection of ondansetron, a 5-HT3 receptor antagonist, partially reversed paclitaxel-induced pain, indicating that 5-HT3 receptors were involved in descending serotoninergic modulation of spinal pain processing. Conclusion: The results suggest that activation of the p38 MAPK pathway in the RVM leads to increased RVM Tph expression and descending serotoninergic projection to the spinal dorsal horn and contributes to the persistence of CIPN via spinal 5-HT3 receptors.

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Attenuation of hyperalgesia responses via the modulation of 5-hydroxytryptamine signalings in the rostral ventromedial medulla and spinal cord in a 6-hydroxydopamine-induced rat model of Parkinson’s disease

Cited by 33 publications

References 58 publications

Electrophysiological Properties of Substantia Gelatinosa Neurons in the Preparation of a Slice of Middle-Aged Rat Spinal Cord

Electrophysiological Properties of Substantia Gelatinosa Neurons in the Preparation of a Slice of Middle-Aged Rat Spinal Cord

Potential of animal models for advancing the understanding and treatment of pain in Parkinson’s disease

<p>Selective Ablation of Descending Serotonin from the Rostral Ventromedial Medulla Unmasks Its Pro-Nociceptive Role in Chemotherapy-Induced Painful Neuropathy</p>

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