Sensory Afferents for Deep Pressure Sensation

Objective:

The sensory basis of non-painful deep pressure sensation is not known. We recently found that innocuous pressure sensation is eliminated in rare sensory neuronopathy patients with a specific loss of A-beta fibers, strongly suggesting that A-beta fibers underlie the ability to sense deep pressure. In addition, we and others have shown that deep pressure touch (observed in hugs and massage) frequently conveys a sense of pleasantness. The current study aims to examine the role of A-beta fibers in the perception of deep pressure touch including both its intensity and the pleasant affect it often elicits. This study constitutes the second study of the K99 phase of a K99/R00 grant application awarded to Dr. Laura Case by National Center for Complementary and Integrative Health (NCCIH).

Study Population:

Up to 24 healthy participants will be enrolled in the study with a goal of 12 completers. Participants will be invited based on previous screening and participation in our studies.

Design: Participants will undergo an ischemic-compression block. Sensory stimuli will be administered at frequent intervals to capture the loss of sensation related to A fibers as the block progresses. Before and after A-beta-associated sensations have been lost, the perception of deep pressure will be tested. Participants will rate the intensity and pleasantness of the pressure. Ratings of pain and discomfort will be collected throughout the study session.

Outcome measures: Primary outcome; Rating of intensity of deep pressure on the blocked arm before versus after loss of A-beta sensation, compared to ratings on the unblocked arm.

Secondary outcomes: 1) Rating of pleasantness of deep pressure on the blocked arm after loss of A-beta sensation, compared to ratings on the unblocked arm; 2) Ratings of intensity and pleasantness of gentle brushing on the blocked arm after loss of A-beta sensation, compared to ratings on the unblocked arm.

• INCLUSION CRITERIA:

All subjects must be:

• Between 18 and 50 years old.
• Fluent in English.
• Able to provide written informed consent.
• Enrolled in 16-AT-0077, Clinical and Scientific Assessment of Pain and Painful Disorders

Exclusion criteria

• Unable to comply with study procedures.
• Have used recreational drugs in the past 30 days.
• Pregnancy or breastfeeding.
• Congenital upper limb deficiency or amputation.
• Peripheral neuropathy, dermatological condition such as scars or burns, or has had a tattoo in the testing region within the previous four weeks that might influence cutaneous sensibility.
• Current chronic pain condition or has had chronic pain in the past year (painful condition lasting more than six months), including ongoing treatment with medications for neuropathic pain (e.g. gabapentin, tricyclic antidepressants, pregabalin, tramadol).
• Major medical condition, such as kidney, liver, cardiovascular (including blood clots, hypertension, preexisting cardiac arrhythmia, lymphadenopathy), autonomic, pulmonary, or neurological problems (e.g., seizure disorder) or a chronic systemic disease (e.g., diabetes) or Raynaud s disease.
• Personal history or first-degree family history of blood clots or clotting and circulatory disorders
• History of a seizures or first-degree family member with a seizure disorder
• High (>140/90) or low (<90/60) blood pressure
• Current and untreated diagnosis of major depression, post-traumatic stress syndrome, bipolar disorder, psychosis, anxiety or panic disorder, alcohol or substance use disorders
• History of fainting with blood draws
• Any medical counter-indications to the nerve blocks.
• Participant s arm unable to fit in inflated arm blood pressure cuff
• Participant has taken any pain medication other than an over-the-counter NSAIDs or acetaminophen within the last month or for more than one month on a continual basis within last six months.
• Used topical pain-relieving creams in the testing area within 24 hours of testing or non-steroidal anti-inflammatory drugs (NSAIDS), (e.g. aspirin, ibuprofen, acetaminophen, or naproxen) within 3 days of testing
• Recent use of medications that increase risk of seizures (e.g. antidepressant Wellbutrin or antipsychotic Haldol)
• NIH employees who are subordinates, relatives, or co-workers of the investigators, or NCCIH DIR employees.

Exclusion criteria

FOR INDIVIDUAL STUDY SESSION:

• Shows signs of alcohol withdrawal syndrome, or has behavioral signs of intoxication: will be excluded immediately and not have the possibility to reschedule their session.
• Used topical pain-relieving creams in the testing area (e.g. methylsalicylate, capsaicin) within 24 hours of testing or used non-steroidal anti-inflammatory drugs (NSAIDS, e.g. aspirin, ibuprofen), acetaminophen, or naproxen within 3 days of testing.