Pain in Parkinson's disease (PD) is increasingly recognized as a major factor associated with poor healthrelated quality of life. However, classic therapeutic drugs supplying dopamine have limited therapeutic effect on PD related pain. This suggests that there is a mechanism outside the dopamine system that causes pain in PD. Our previous study has demonstrated that 6-OHDA induced PD model manifested hyperalgesia to thermal and mechanical stimuli and decreased serotonin (5-HT) contents in the spinal dorsal horn (SDH). Several 5-HT receptor subtypes have been con rmed to be associated with nociception in the spinal cord, such as 5-HT1A receptor, 5-HT1B receptor, 5-HT2 receptor, 5-HT3 receptor, and 5-HT7 receptor. Most researches have shown that 5-HT1A receptor and 5-HT3 receptor played a key role in pain transmission in the spinal cord. Thus, we hypothesize that hyperalgesia of 6-OHDA rats may be related to increased excitability of SDH neurons and the functional change of 5-HT3 receptor may reverse the hyperalgesia of 6-OHDA rats and decrease cell excitability of SDH neurons. To test this hypothesis, we used whole-cell patch-clamp and pharmacological methods to evaluate the effect of 5-HT3 receptor and 5-HT1A receptor on the hyperalgesia of 6-OHDA rats. The results suggested that increased excitability in SDH neurons could be reversed by 5-HT3 receptor antagonist ondansetron (20 µmol/L), but not 5-HT3 receptor agonist M-CPBG (30 µmol/L), 5-HT1A receptor antagonist 8-OH DPAT (10 µmol/L)and agonist WAY-100635 (10 µmol/L). Intrathecal injection with ondansetron (0.1 mg/kg) but not M-CPBG (0.1 mg/kg), 8-OH DPAT (0.1 mg/kg) and WAY-100635 (0.1 mg/kg) signi cantly attenuated the mechanical hyperalgesia and thermal hyperalgesia of 6-OHDA rats. Therefore, the present study suggests that inhibition of 5-HT3 receptor relieves hyperalgesia in PD rats by reducing the excitability of SDH neurons. Our study provides a novel mechanism or therapeutic strategy for pain in patients with PD.

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Pain in Parkinson’s disease (PD) is increasingly recognized as a major factor associated with poor health-related quality of life. However, classic therapeutic drugs supplying dopamine have limited therapeutic effect on PD related pain. This suggests that there is a mechanism outside the dopamine system that causes pain in PD. Our previous study has demonstrated that 6-OHDA induced PD model manifested hyperalgesia to thermal and mechanical stimuli and decreased serotonin (5-HT) contents in the spinal dorsal horn (SDH). Several 5-HT receptor subtypes have been confirmed to be associated with nociception in the spinal cord, such as 5-HT1A receptor, 5-HT1B receptor, 5-HT2 receptor, 5-HT3 receptor, and 5-HT7 receptor. Most researches have shown that 5-HT1A receptor and 5-HT3 receptor played a key role in pain transmission in the spinal cord. Thus, we hypothesize that hyperalgesia of 6-OHDA rats may be related to increased excitability of SDH neurons and the functional change of 5-HT3 receptor may reverse the hyperalgesia of 6-OHDA rats and decrease cell excitability of SDH neurons. To test this hypothesis, we used whole-cell patch-clamp and pharmacological methods to evaluate the effect of 5-HT3 receptor and 5-HT1A receptor on the hyperalgesia of 6-OHDA rats. The results suggested that increased excitability in SDH neurons could be reversed by 5-HT3 receptor antagonist ondansetron (20 µmol/L), but not 5-HT3 receptor agonist M-CPBG (30 µmol/L), 5-HT1A receptor antagonist 8-OH DPAT (10 µmol/L)and agonist WAY-100635 (10 µmol/L). Intrathecal injection with ondansetron (0.1 mg/kg) but not M-CPBG (0.1 mg/kg), 8-OH DPAT (0.1 mg/kg) and WAY-100635 (0.1 mg/kg) significantly attenuated the mechanical hyperalgesia and thermal hyperalgesia of 6-OHDA rats. Therefore, the present study suggests that inhibition of 5-HT3 receptor relieves hyperalgesia in PD rats by reducing the excitability of SDH neurons. Our study provides a novel mechanism or therapeutic strategy for pain in patients with PD.