Painful symptoms are also part of the opioid withdrawal syndrome, and increased pain sensitivity can be measured in chronic pain and addict populations when the serum drug concentrations are near their nadirs [35,60]. Rodents display nociceptive sensitization after chronic morphine administration, even without antagonist-precipitated withdrawal. This sensitization is used as a measure of opioid dependence [36,37]. In addition to blocking naloxone-induced withdrawal behaviors, ondansetron effectively reversed the spontaneous hyperalgesia in our morphine-dependent mice. Other investigators have reported that spinal 5-HT3 receptors may modulate OIH as well [61]. These findings emphasize that the 5-HT3 is involved in at least two objectively quantifiable manifestations of opioid dependence.
