OBJECTIVES: 1) To measure the prevalence of precipitating events in pediatric chronic pain patients and 2) to compare pain and functional disability outcomes at evaluation and 4-month follow-up by presence and type of precipitating event. METHODS: Precipitating events (e.g., injury) were coded from the medical record for 401 youth (6-19) who presented to a tertiary care chronic pain clinic. Four-month follow-up disability and pain were collected for 187 patients. In addition to frequency of events, we examined differences in pain and disability measures by event type at evaluation and follow-up using multiple statistical analysis strategies. RESULTS: Two-thirds of patients had a precipitating event prior to pain onset. Injury was the most common (55%), followed by chronic disease (23%), infection/illness (12.8%), and surgery (7.5%). Patients whose pain was triggered by injury reported the highest average pain levels, F(3, 340)=2.67, p<.05 and functional disability, F(3, 295)=3.54, p<.05. There were multiple cases of event groups that had significantly different baseline and follow-up psychological measures when compared to the rest of the patient population. Trajectories of pain and disability did not differ between patients with and without a precipitating event. Patients with injuries reported greater improvement in functional disability at follow-up (time x injury) F(1, 183)=4.88, p<.05 whereas patients with chronic disease reported less improvement in disability (time x chronic disease), F(1, 183)=5.49, p<.05. No other interactions were significant for disability or pain. CONCLUSIONS: A majority of patients had experienced some form of precipitating event prior to their pain onset, and the presence of a precipitating event had varied effects on the treatment outcomes of patients at four-month follow-up. Although patients with injuries presented with greater disability and pain, they had significantly more improvement, while chronic disease patients were less likely to improve in terms of functional disability. Type of precipitating event appears to be associated with treatment response and can inform clinical prognoses.

Pain is the primary reason why patients seek medical care and there is a great unmet need for the development of pain relieving medications. The treatments that are currently available either have limited efficacy or are accompanied by a multitude of unwanted side effects. However, discovering novel therapeutics for the treatment of pain has been challenging. Part of the reason for this may be that that the ways in which pain is assessed in the preclinical setting are different from the way that it is evaluated clinically in human trials. The most common method for evaluating pain in preclinical models is to measure responses to evoked stimuli. However, a change in the threshold of response to evoked pain likely does not measure whether the unpleasant component of pain has actually been reduced. The most clinically relevant question for pain is whether the treatment actually makes the patients "feel better". Here, we demonstrate that the aversiveness of pain can be captured using motivated behavior to seek pain relief. We used conditioned place preference (CPP) to establish that animals with ongoing pain will seek a context that has been paired with effective pain relief, likely as a result of negative reinforcement. These studies allowed for mechanistic investigation. Our results show that: 1) effective pain relief can be achieved by either blocking noxious peripheral input or by directly attenuating pain related unpleasantness in the brain, and 2) pain relief is rewarding and activates the reward circuitry. These studies provide a basis for development of a future platform for drug discovery for pain.