Background and aims: The serotonin 2A (5-HT2A) receptor has been described as facilitation mediator of spinal nociceptive processing leading to increased spinal nociceptive transmission and central sensitization. Contribution of 5-HT2A single nucleotide variants (SNV) on neuropathic pain susceptibility and sensory perception of neuropathic pain patients is largely unknown. The aim of this study was to elaborate whether selected 5-HT2A variants influence pain susceptibility in general and/or the extent of sensory abnormalities in neuropathic pain patients.
Methods: This study included 240 neuropathic pain patients and 248 healthy volunteers. Patients were phenotypically characterized using quantitative sensory testing (QST) and divided into two subgroups (gain/loss of function). Patients and controls were genotyped by pyrosequencing of three SNVs in 5-HT2A (452C>T, 102C>T, -1438G>A). Differences in genotype distribution between patients and controls were analyzed using Chi-squared test. Differences in somatosensory profiles and in frequencies of abnormal QST parameters of patients were assessed. Statistical analysis was performed using SPSS 22.0.
Results: Due to not fulfilled Hardy-Weinberg equilibrium 452C>T was excluded for analysis. There was no significant difference in 102C>T and linked -1438G>A genotype distribution of patients and controls. However, the 102C>T variant allele was associated with lower thresholds for noxious mechanical stimuli, indicating mechanical hyperalgesia and increased mechanical pain sensitivity (MPT; p=0.002; MPS; p=0.009).
Conclusion: There was no evidence for a direct association between 5-HT2A variants and presence of neuropathic pain. However, the 102 C>T variant was associated with central sensitization of the nociceptive system (pinprick hyperalgesie) supporting an involvement of 5-HT2A in pain facilitation

SEROTONIN RECEPTOR 2A (5-HT2A) POLYMORPHISMS ARE ASSOCIATED WITH PINPRICK HYPERALGESIA IN NEUROPATHIC PAIN PATIENTS