Endogenous Opioid Response to Injections

Nerve blocks are commonly used in pain medicine to diagnose painful conditions and predict response to invasive procedures and surgeries. Placebo responses may cripple clinicians' ability to interpret responses to nerve blocks and guide patient care, when reported pain relief is due to placebo rather than the nerve block. Existing methods to assess placebo response in clinical practice are limited and indirect. The area that is most explored is in the diagnosis of pain from the facet joints of the spine and relies on an indirect signal from repeated diagnostic injections. Lumbar medial branch radiofrequency neurotomy (LMBRN) is commonly used to treat low back pain and can lead to large improvements in pain and disability. There is a high failure rate of LMBRN even after a series of controlled prognostic injections called lumbar medial branch nerve blocks (LMBB) with local anesthetic. The discrepancy between response to LMBB and LMBRN has been attributed to the confounding of pain relief from the nerve block with pain relief from the placebo response. Endogenous opioids (EO), substances produced within the human body that bind to opioid receptors and produce opioid analgesia, are likely responsible for most of the placebo response caused by LMBB. This study will use naloxone, an opioid receptor antagonist, to completely block the activity of EOs in patients. First, the pain relief after LMBB will be recorded - this is a combination of the effect of the nerve block and EO released in the placebo response. Normal saline will be infused, as an internal control for the state of receiving an infusion. Naloxone will then be infused, reversing EO-dependent placebo analgesia - the analgesia remaining will be from the nerve block. Finally, clinical outcomes from LMBRN will be collected to determine whether using naloxone with LMBB can improve prediction of outcomes with LMBRN. Naloxone will be used to probe a mechanism of procedurally-induced endogenous-opioid mediated placebo analgesia. No IND is pursued in this study. These data will provide detailed parameters of placebo response from LMBB, improving interpretation of LMBB for estimation of prevalence of zygapophyseal joint pain and for prognostication of LMBRN. Furthermore, if this methodology of EO reversible analgesia is feasible for investigation of placebo from LMBB, it will be more broadly investigated in diagnostic and prognostic injections used in interventional pain management.