Clinical Research Directory

Impact of Repeatedly-Administered THC-cannabis on Experimental Pain and Abuse Liability in Humans

Chronic pain is a significant public health concern in the U.S., for which prescription opioids have historically been the standard treatment. This has resulted in striking rates of opioid use disorders and fatal overdoses. Identifying non-opioid medications for the management of chronic pain with minimal abuse liability is a public health necessity, and cannabinoids are a promising drug class for this purpose. More than 80% of medicinal cannabis users report pain as their primary medical indication, and they report experiencing minimal psychoactive effects. However, there are few well-controlled human laboratory studies assessing cannabis' efficacy for pain in the context of abuse, and even less is known regarding the effects of daily repeated use of cannabis on pain and its relationship to abuse liability. Carefully controlled research is needed. The proposed within-subjects, placebo-controlled 16-day crossover inpatient human laboratory study (N = 20 healthy cannabis users; 10 men, 10 women) will address three important gaps in our understanding of the potential therapeutic utility of cannabis for pain: 1) Does tolerance develop to repeated, daily smoked cannabis administration on measures of experimental pain and abuse liability; 2) If so, is tolerance reversed during the 7 days of abstinence from active-THC cannabis; 3) Does abrupt abstinence from active cannabis increase experimental pain sensitivity, i.e. hyperalgesia, relative to baseline, and do these effects parallel measures of cannabis withdrawal such as disrupted mood and sleep? Two distinct modalities of experimental pain will be assessed: The Cold Pressor Test (CPT) and Quantitative Sensory Testing Thermal Temporal Summation (QST-TTS). Throughout the study, experimental pain and abuse-related effects will be assessed, as will sleep and subjective mood assessments.

Dextromethorphan Effect on Central Sensitization to Pain in Healthy Volunteers

The aim of this study is to assess the anti-hyperalgesic effect of dextromethorphan in healthy volunteers compared to placebo.

Effect of Ultra-low Dose Naloxone on Remifentanil-Induced Hyperalgesia

The purpose of this study is to evaluate whether using ultra-low dose naloxone, an opioid antagonist, has the potential to block remifentanil-induced hyperalgesia and tolerance following surgery. There are 3 study groups: (1) low dose remifentanil (LO, 0.1 micrograms/kg/mL), (2) high dose remifentanil (0.4 mg) combined with placebo (HI, 0.4 micrograms/kg/mL), or (3) high dose remifentanil (0.4 mg) combined with ultra-low dose naloxone (HN, 0.004 micrograms/kg/mL naloxone). The hypothesis of the study is that occurrence of remifentanil-induced hyperalgesia (low score in mechanical pain threshold) in the HN group will be lower than in the HI group.

Session-Order Sensitivity of TS and OA in a Capsaicin Crossover Model

Temporal summation (TS) and offset analgesia (OA) are widely used psychophysical endpoints in pain research that index different components of central nociceptive processing. While crossover designs are commonly used in experimental pain studies to reduce between-participant variability, the design-stability of these endpoints under repeated testing during experimental sensitisation is not well characterised. This study compared the design-stability of mechanical TS (Sumscore) and offset analgesia magnitude (OffA) in a two-period, vehicle-controlled crossover trial of capsaicin-evoked secondary hyperalgesia in healthy adults. The primary aim was methodological: to determine whether session-order effects differ between TS and OffA when these are used as outcome measures in two-period crossover designs of capsaicin-induced central sensitisation. Topical capsaicin was used as a reversible experimental intervention to create a controlled, transient state of secondary hyperalgesia rather than as a therapeutic intervention. The study informs endpoint selection in future quantitative sensory testing (QST) crossover trials.

STTEPP: Safety, Tolerability and Dose Limiting Toxicity of Lacosamide in Patients With Painful Chronic Pancreatitis

The investigators propose to conduct a dose-escalation trial of an FDA-approved antiepileptic drug, lacosamide, added to opioid therapy in patients with chronic abdominal pain from chronic pancreatitis (CP). This pilot trial will test the feasibility of the study design and provide reassurance regarding the tolerability and safety of lacosamide used concomitantly with opioids in this patient population to reduce the condition known clinically as opioid-induced hyperalgesia (OIH).

Local Anesthetic Infiltration to Prevent Postoperative Pain After Lumbar Surgery

Posterior lumbar arthrodesis causes severe postoperative pain, hampering patients's postoperative reconvalescence especially functional rehabilitation. Efficient and safe methods for postoperative analgesia are, therefore, mandatory. The application of opioids are the most frequently used therapies for postoperative pain relief but it very often results side effects. Local anesthetic wound infiltration is widely recognized as a useful adjunct in a multimodal approach to postoperative pain management. In the setting of spine surgery, a single bolus administration of a local anesthetic is a useful method (with a reduction in parenteral morphine consumption during the 48 first hours) but has a limited effect because of its short duration of action. Prolonged administration through a multi-holed catheter positioned by the surgeon at the end of the procedure could increase the duration of action and may thereby improve the efficacy of local wound infiltration. Easy and effective, this new modality of administration has expanded the indications for parietal infiltrations toward major painful procedures. We designed this study to determine whether local anesthetic (compared with saline solution) continuous wound infiltration during the first two days after posterior lumbar arthrodesis on degenerative spine, could improve postoperative analgesia at short-term but particularly at mid-term (two months) and long-term (six months), in order to decrease postoperative lumbar pains (resulting in best life quality, opioid consumption limited and rehabilitation hastened) and postoperative hyperalgesia areas. The postoperative analgesic and antihyperalgesic efficacies; the postoperative rehabilitation at mid-term and long term, and the safety of opioid administration and multi-holed parietal catheter will be compared in the two groups (control and study).

Evaluation of a Patient-Centred, Multidisciplinary Opioid Tapering Program for Individuals With Chronic Non-Cancer Pain on Long Term Opioid Therapy

Chronic pain management is complex, with healthcare providers historically relying on prescribing opioid medications such as morphine. Although opioids may partially improve pain, there are risks associated with them as well, including pain worsening, side effects, addiction and overdose. It is now understood that the management of chronic pain is more effective when multiple healthcare team members work together and incorporate multiple strategies instead of focusing solely on medications. An example of an effective, non-drug strategy for pain is a service offered by clinical psychologists called "Acceptance and Commitment Therapy" - or ACT - which empowers individuals, to implement alternative ways of thinking about and reacting to pain and its effect on their lives. Canada has responded to the opioid overdose crisis with new guidelines that encourage physicians and those suffering from chronic pain to aim for lower opioid doses whenever possible, a process often referred to as "tapering." Unsurprisingly, tapering opioids is often difficult for patients to consider, primarily due to misconceptions that it will cause more harm than good. This project aims to address these misconceptions by developing and offering an all-day educational workshop for patients, co-presented by a healthcare team (clinical psychologists, pharmacists and physicians), to provide in-depth information on opioid related risks and misconceptions, as well as a large component focusing on ACT training. Investigators then want to see if these sessions change individual attitudes towards opioid tapering and if it improves willingness and ability to successfully reduce opioid doses to a safer level.

Investigation on the Status Quo of Hyperalgesia in Patients After Thoracoscopic Operation and Study on the Effect of Intraoperative Intervention

To explore the status quo and influencing factors of hyperpain in patients after thoracoscopic surgery, and to explore the effect of earphone sound isolation during combined operation of flurbiprofen axidate and binaural beat music played by earphone during combined operation on the intervention of hyperpain after thoracoscopic surgery.

Electroacupuncture Pain Treatment, Mechanical Hyperalgesia, Quality of Life & Expression of Mu+ B Cells in Fibromyalgia

Fibromyalgia (FM) is a complex, multifactorial syndrome characterized by widespread chronic pain with hyperal- gesia and allodynia and a constellation of somatic and psychological manifestations, including fatigue, sleep dis- orders, depression, anxiety, gastrointestinal and cognitive disorders. FM is now recognized as one of the most common chronic pain conditions and its management remains a challenge for patients and healthcare profes- sionals. The fact that FM is associated with chronic pain without any obvious peripheral tissue damage has given rise to the concept of nociplastic pain with evidence of dysfunction in mono-aminergic neurotransmission, lead- ing to elevated levels of excitatory neurotransmitters and decreased levels of serotonin and norepinephrine in the spinal cord at the level of descending anti-nociceptive pathways. Additionally, dopamine dysregulation and altered activity of endogenous cerebral opioids have been observed in FM. Recent European guidelines on FM treatment emphasize that there should be a comprehensive assessment of patient's pain, function and psychosocial context. It is recognized that there are profound and fundamental problems associated with the pain assessment tools in common use, as most of these represent an attempt to reduce a multidimensional experience to a coarse unidimensional measure. Use of multiple tools for sub- jective and objective assessment of pain may reflect more accurately patient's pain experience. Furthermore, tracing a biologic pain marker in FM patients would facilitate both the initial assessment of pain and the re- sponse to treatment. Management of pain in FM patients should focus first on non-pharmacological modalities. Acupuncture therapy is an effective and safe treatment and exerts its analgesic effect through activation of pe- ripheral and central pain control systems with the release of β-endorphins, enkephalins, dynorphins, serotonin, norepinephrine, γ-aminobutyric acid or ATP. The aim of our study is to assess initially reported pain and evaluate the effectiveness of electroacupuncture (with or without diet modifications) on the "whole experience of pain" in FM patients in a multimodel assessment frame.