Highlights Ribosome display used for recombinant antibody selection and scFv generation targeting CCK-BR. Engineered scFv have stronger affinity and increased tissue penetrability due to smaller size. Single dose scFv reduces hypersensitivity, anxiety- and depression-like behavior in two models. Reduced neuronal firing frequency in TG primary neuronal cultures treated in vitro . CCK-BR scFv is ideal for neuropathic pain with both nociceptive and emotional components.

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The intrathecal drug delivery system (IDDS) is successfully utilized for the treatment of chronic pain conditions; however, they are associated with complications related to human error and system failure. A case report is presented of a patient with opioid withdrawal (OW) secondary to assumed catheter microfracture. Interrogation of the IDDS allowed for the collection of pre-and post-treatment/stabilization cerebrospinal fluid (CSF), which is used to investigate the possible physiological determinants of OW.A 46-year-old female with a history of low back pain after traumatic low back injury status post-IDDS placement for failed back surgery syndrome presented with signs and symptoms concerning for OW. After every other possible explanation was ruled out, it was hypothesized that there may be IDDS catheter microfracture(s), and catheter replacement led to symptom resolution. There were no significant differences in cytokine levels tested in pre-CSF versus post-CSF samples. Whole-cell patch-clamp electrophysiology analysis of human-induced pluripotent stem cell-derived nociceptors after treatment with pre-and post-CSF samples demonstrated modulation of action potential waveform.In patients presenting with acute OW attribution IDDS malfunction, catheter microfracture must be in the differential, and non-conventional interrogation of the IDDS catheter should be considered. The possible differences in pre-CSF and post-CSF may be more complicated than previously postulated, as there were no significant differences in cytokine profiles; however, treatment of in vitro neurons with pre-and post-CSF resulted in differential neuronal excitability, which may account for some of the symptoms of OW.

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