Optimising Management of acute pain in Opioid Substitution Therapy patients: A pilot laboratory randomised study

There are three participant groups. i) Participants on methadone ii) Participants on buprenorphine (or buprenorphine+naloxone) iii) A healthy control group. The procedures for the first two participant groups (those on methadone and those on a buprenorphine product) will attend four sessions each, in random order, with five days washout between each session. Each session is approximately three hours long. The cold pressor test is administered two hours after baseline. The four sessions (which are in random order) are: (1) STANDARD OPIOID MAINTENANCE MEDICATION DOSE ONLY Standard methadone oral liquid (the participants own regular dose) OR buprenorphine (+/- naloxone) (the participants own regular dose of buprenorphine sublingual tablet or buprenorphine plus naloxone (4:1 ratio) depending on what the participants usual OST medication is. NB naloxone is only given as part of the Suboxone combination product if that is the participants usual opioid medication, naloxone is not absorbed by the sublingual route. Naloxone is not given to other participants unless it is a part of their routine opioid agonist maintenance medication. (2) THIRTY PERCENT INCREASE OF STANDARD OPIOD MAINTENANCE DOSE In this session a 30% increase in the participants own standard methadone liquid dose or buprenorphine (+/- naloxone) sublingual tablet or film dose is given. The actual dose will depend on participants base dose. (3) OXYCODONE DOSE In this session the participants standard methadone oral liquid dose or buprenorphine (+/- naloxone) sublingual dose plus oral immediate release oxycodone tablets, dose to be equivalent to 30% of usual maintenance methadone / buprenorphine (+/- naloxone) (Note - the actual dose will depend on the participants regular dose of methadone or buprenorphine which will be used to calculate the oxycodone dose). (4) GABAPENTIN DOSE the participants standard methadone oral liquid dose / or buprenorphine (+/- naloxone) sublingual dose plus 600mg gabapentin oral tablet. The healthy control (non-methadone, non-buprenorphine) subjects will attend the study laboratory for three 3-hour study sessions, each separated by at least 5 days. At each session, the cold pressor test will be conducted 2 hours after baseline. In random order each participant will receive (1) placebo (either matched placebo for gabapentin or matched placebo for oxycodone or both, depending on active condition) (2) immediate release oxycodone 5mg oral tablet (3) 600mg gabapentin oral tablet Cold Pressor Procedures: Acute pain response will be measured the two hour time point using a standardized cold pressor trial. With this widely used experimental pain induction method, a body limb (typically the arm) is immersed cold water, reliably producing an aching pain of clinical quality and intensity. Cold Pressor testing approach: The participants will be seated in a comfortable chair, and asked to roll up their sleeve and remove watches or jewelry from their non-dominant arm and hand. Participants will then place their forearm (to above the elbow) into the cold water bath with fingers wide apart. No contact will be made with the side or bottom of the container. As soon as the limb is fully immersed, timing will begin. A water pump is placed in the cold-water container to prevent laminar warming around the immersed limb. Participants will not be spoken to during the cold-water immersion in order to minimize any distraction or cues for time that could adversely influence pain detection and tolerance levels. Participants will be told to inform the research staff when (a) pain is initially detected (threshold). Then they will be asked to keep the immersed limb in the container until pain can no longer be tolerated and then remove their arm (b) the time when they remove their arm from the bath is recorded by the research staff (tolerance).