Chronic pain can result from injured or inflamed nerves, as occurs in people suffering from sciatica and CRPS. These nerve injuries or regions of nerve irritation are often the cause of pain in these conditions, but the current diagnostic tools are limited in pinpointing the area of origin. Several studies have implicated involvement of sigma-1 receptors in the generation and perpetuation of chronic pain conditions, others are investigating anti sigma-1 receptor drugs for the treatment of chronic pain. Using the sigma-1 receptor (S1R) detector and experimental radiotracer [18F]FTC-146 and positron emission tomography/magnetic resonance imaging (PET/MRI) scanner, the researchers may potentially identify the source of pain generation in patients suffering from complex regional pain syndrome (CRPS) and chronic sciatica. The ultimate goal is to assist in the optimization of pain treatment regimens using an [18F]FTC-146 PET/MRI scan.

The study is not designed to induce any physiological/pharmacological effect.

Participants are either pain free (control) or will be recruited based on established criteria for sciatica or CRPS. A signed consent will be obtained from willing participants.

For the PET/MRI scan, the participants will be injected with [18F]FTC-146 intravenously. After injection, simultaneous PET and MRI scans will be acquired using a hybrid PET/MRI scanner. Throughout scanning, participants will be monitored for blood pressure, temperature, heart rate and pulse oximetry. Participants will be asked to void their bladder as frequently as they can to reduce radiation exposure. Following the scan, participants will be contacted to check for adverse drug events, and any events will be recorded in the case report.

Evidence in the literature points strongly toward an involvement of S1 receptors in nervous system inflammation, which is known to be an important biologic disease/disorder mechanism for maintenance and perpetuation of chronic pain.

The main purpose of this research study is to image and identify activated pain pathways in human subjects using [18F]FTC-146 PET/MRI.

Inclusion Criteria:

General:

• At least 18 years of age
• Either male or female

Sciatica:

• History of pain shooting down a leg below the knee, to the foot or toes
• Visual analog scale (VAS) at enrollment of >4 with leg pain greater in intensity than the back pain
• Focal disc herniation on MRI correlating with radicular symptoms defined as pain or paresthesias into the leg.
• Examination with correlating radicular signs defined as any of the following:
• pain reproduction with straight-leg-raising (pain shooting down the leg with less than 60 degrees elevation)
• radicular pattern sensory changes (such as numbness or paresthesias) in the same area as pain
• signs of radiculopathy (weakened hallux extension and/or Achilles tendon reflex)
• The above inclusion criteria can be met OR individuals who have been determined to have a very high clinical suspicion of having Sciatica as determined by the referring pain specialist can be included. This suspicion will be documented in the patient's medical record.

CRPS:

• Disease duration of 6 months or longer

• Continuing pain, which is disproportionate to any inciting event

• Must report at least one symptom in three of the four following categories:

  1. Sensory: Reports of hyperesthesia and/or allodynia
  2. Vasomotor: Reports of temperature asymmetry and/or skin color changes and/or skin color asymmetry
  3. Sudomotor/Edema: Reports of edema and/or sweating changes and/or sweating asymmetry
  4. Motor/Trophic: Reports of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin)

• Must display at least one sign at time of evaluation In two or more of the following categories:

  1. Sensory: Evidence of hyperalgesia (to pinprick) and/or allodynia (to light touch and/or temperature sensation and/or deep somatic pressure and/or joint movement)
  2. Vasomotor: Evidence of temperature asymmetry ( >1°C) and/or skin color changes and/or asymmetry
  3. Sudomotor/Edema: Evidence of edema and/or sweating changes and/or sweating asymmetry
  4. Motor/Trophic: Evidence of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin)

• There is no other diagnosis that better explains the signs and symptoms

• For research purposes, diagnostic decision rule will be at least one symptom in all four symptom categories and at least one sign (observed at evaluation) in two or more sign categories.

• The above inclusion criteria can be met OR individuals who have been determined to have a very high clinical suspicion of having CRPS as determined by the referring pain specialist can be included. This suspicion will be documented in the patient's medical record.

Exclusion Criteria:

General:

• Another active disorder which could explain the symptoms in the opinions of the investigator
• Failure to give informed consent
• Presence of MRI-incompatible materials/devices
• Any medication that may affect pain or 18F-FTC-146 uptake or adverse drug interactions with steroids or amino amide local anesthetics (e.g. lidocaine, bupivacaine, ropivacaine)
• Pregnant or nursing
• Ongoing menstrual period
• Severe comorbid conditions
• Unable to read or complete questionnaires in English
• Any other condition, which in the opinion of the investigator would impede compliance or hinder completion of the study

Sciatica:

• Any condition that may interfere with interpretation of 18F-FTC-146 uptake in the region of the pelvis, thighs or lower spine including, but not limited to,

  1. Spinal, hip or pelvic surgery or prosthesis

  2. Cancer

  3. Radiation therapy

  4. Autoimmune disorders

  5. Current infections

  6. Inability to void bladder completely, such as in prostatic enlargement

  7. Any urinary retention, such as in outlet obstruction, hydronephrosis etc.

  8. Cauda equina syndrome

  9. Developmental spinal deformities

  10. Scoliosis >20 degrees

  11. Spondylolysis

  12. Vertebral fractures

  13. Inflammatory spondylopathy

  14. Prior lumbar surgery

      CRPS:

• Presence of current or past pulmonary, hepatic, renal disease, arthritis, hematopoietic, and neurological diseases not related to CRPS.