Remote Ischemic Preconditioning Mechanism Study
Condition: Pain
MeSH terms: Ischemia
Study type: Interventional
Phase: Early Phase 1

Summary: 
      This research is being done because pain is a significant problem for patients with a variety
      of medical problems and following surgery or traumatic injury. Currently available pain
      medications may not relieve all types of pain or may relieve pain only at doses that produce
      side effects and potential complications.

      Although Remote Ischemic Preconditioning (RIPC) appears promising, there remain several
      unanswered questions about how it works. This research trial will help determine how RIPC may
      activate the bodies natural pain control system. The goals of this study are to see if RIPC
      has any effect 1) on a small area of skin that will be expose to a small amount of UV- B
      radiation (a mild sunburn), 2) on acute thermal heat temperatures that will be applied to
      skin, and 3) on the sunburn-like sensation to light touch after putting capsaicin cream (the
      active ingredient in hot chili peppers) on skin.

      Remote ischemic preconditioning is done by inflating a balloon (very similar to a blood
      pressure cuff) on the leg until it blocks blood flow for a few minutes. The cuff is then
      deflated and blood flow resumes. The process is repeated up to three times. This procedure
      causes the body to increase its natural pain relief system that may help to decrease the
      amount of postsurgical pain.
    

Detailed description: 
      The purpose of this pilot study is to determine whether RIPC effects peripheral
      sensitization, central sensitization or both and determine effect size since there is no data
      regarding the presumed effect. These issues cannot be easily sorted out in patients
      experiencing postoperative pain and hypersensitivity, since surgery affects both components.
      In order to address this purpose the investigators will examine, in healthy volunteers, the
      effect of RIPC on a manipulation which generates hypersensitivity by an exclusive peripheral
      mechanism (ultraviolet B (UV-B) burn) and a manipulation which generates hypersensitivity by
      an exclusive central mechanism (topical capsaicin). Understanding the sites at which RIPC
      reduces the amplification of pain after injury will be useful in determining where it would
      be most logically applied clinically and in guiding preclinical mechanistic studies.
    

Intervention name(s): Remote Ischemic Preconditioning, Capsaicin, UV-B
Intervention type(s): Device
Intervention description(s): The participants will have one disposable tourniquet applied to the left mid thigh by research personnel. The participants will then be randomized to the treatment group or sham group. The treatment group will receive 3 cycles of RIPC to the left lower leg by occluding blood flow at the thigh with a pneumatic cuff. Each cycle will consist of 5 minutes of ischemia by inflating the cuff to 300 mmHg followed by 5 minutes of reperfusion. The sham group will have the cuff inflated to no more than 15mmHg for three cycles as described above. Areas of hypersensitivity and allodynia will be obtained every 40 min for 280 min following the end of capsaicin application.
Intervention MeSH terms: Capsaicin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Remote Ischemic Preconditioning; Nociception; Central Sensitization; Peripheral Sensitization