PK Sampling After IV Oxytocin and Effects on Sensory Function in Healthy Volunteers
Condition: Chronic Pain
MeSH terms: Chronic Pain
Study type: Interventional
Phase: Phase 4

Summary: 
      The primary goal of this protocol is to model change in oxytocin concentrations in plasma
      after intravenous (IV) administration. Additional measurements will be performed on sensory
      function that could be influenced by oxytocin during later time periods when blood samples
      are widely separated by time. This protocol will describe the pharmacokinetics (PK) of
      intravenous oxytocin in healthy adult men and adult,non-pregnant women. PK samples will be
      obtained after an injection of intravenous oxytocin 10 IU over 60 seconds.

      Blood will be drawn for the PK samples prior to the oxytocin administration and then 11 times
      after administration.

      There are two additional measures which will assess two different aspects of sensory
      function.

      MEASURE 1: Light Touch Frequency Threshold In order to determine the highest frequency that
      specific nerve fibers can respond to, a simple device that produces an oscillatory /
      vibratory stimulus will be used on the hand. The subject places fingertips, palm, and palm
      side of the wrist sequentially and the device is set to slowly decrease the frequency of
      vibration from 1 kHz until the subject first perceives this. This is repeated three times at
      each site and takes less than 5 minutes in total. This will be performed before the oxytocin
      administration and 6 times after the administration of IV Oxytocin.

      MEASURE 2: Sustained Heat The surface of the skin of the forearm or leg is heated to 113°F
      using a computer controlled thermode for a period of 5 minutes. This will be done before the
      IV Oxytocin and 4 times after the administration. A set of random thermal temperatures
      (98°F-122°F) will also be applied to the skin of the leg or forearm before the IV Oxytocin
      administration and 4 times after administration of IV Oxytocin.
    

Detailed description: 
      The primary goal of this protocol is to model change in oxytocin concentrations in plasma
      after intravenous administration, (oxytocin (Pitocin®), 10 IU) the investigators will also
      acquire tests of sensory function that could be modulated by oxytocin during later time
      periods when blood samples are widely separated by time. There are two measures which will
      assess two different aspects of sensory function.

      MEASURE 1: Light Touch Frequency Threshold Light touch is subserved by a group of myelinated
      peripheral nerves with fast conduction in the Aβ range and which are capable of following
      high frequencies, being responsible for the sensation of vibration. This capability of
      individual nerve fibers to respond with high frequency also underlies our ability to sense a
      light touch moving across the body surface as in brushing.

      In preclinical studies investigators have shown that, following injury, these light touch
      fibers lose their ability to follow high frequencies and, in some cases, no longer respond to
      mechanical stimulation at all. Oxytocin, when perfused around the neuronal cell bodies of
      these Aβ nerve fibers, partially restores their function, including their response to high
      frequency stimulation.

      In order to determine the highest frequency that Aβ nerve fibers can respond to, the
      investigators have created a simple device that produces an oscillatory / vibratory stimulus
      which can be used on the hand. The subject places fingertips, palm, and volar aspect of the
      wrist sequentially and the device is set to slowly decrease the frequency of vibration from 1
      kilohertz (kHz) until the participant first perceives this. This is repeated three times at
      each site and takes under 5 minutes in total.

      The investigators anticipate that oxytocin will have no effect on normal Aβ fibers and that
      this measure will not change after oxytocin administration. This will provide important data
      to contrast with the expected efficacy of oxytocin in the setting of injury, to be studied in
      subsequent protocols.

      MEASURE 2: Sustained Heat As part of a protocol used by the investigators in several studies,
      the surface of the skin of the forearm or leg is heated to 45°C using a computer-controlled
      thermode for a period of 5 minutes. This typically results in a slowly increasing pain
      experience, peaking at 5 minutes in the mild to low moderate range and has been tolerated by
      more than 150 subjects in studies over the past 14 years.

      In an interim analysis of an ongoing clinical study in volunteers, the investigators noted
      that spinal injection of oxytocin, 15 μg (equivalent to 9 IU), that pain from this sustained
      heat was dramatically reduced over the 5 minutes of stimulus presentation. In contrast,
      spinal oxytocin had no effect on the stimulus-response relationship of pain to noxious heat
      over a 42-50°C range when the stimuli were presented for only 5 seconds. These data suggest
      that oxytocin reduces C-fiber mediated signaling of sustained heat pain, likely through a
      spinal site of action.

      Drugs administered spinally have a much higher concentration in cerebrospinal fluid than
      plasma. Nonetheless, spinally administered drugs are typically absorbed to an extent and with
      a time course similar to that after intramuscular injection, and it is conceivable that the
      effect on sustained heat pain investigators are seeing in the spinal study reflect peripheral
      effects via systemic absorption. Thus, if the investigators see a similar reduction in
      response to sustained heat in this protocol of intravenous administration, the investigators
      will conclude that oxytocin is more likely activating peripherally than spinally.
    

Intervention name(s): Oxytocin
Intervention type(s): Drug
Intervention description(s): Single IV administration of oxytocin
Other intervention name(s): Pitocin
Intervention MeSH terms: Oxytocin
Intervention model: Single Group Assignment
Intervention model description: Single intravenous administration of oxytocin (Pitocin®), 10 IU
Masking: None (Open Label)
Primary purpose: Basic Science