Inclusion Criteria:

- Males or females, ages 18 to 55, able and willing to provide written informed consent
to participate in the study.

- Able to read, understand and follow the study instructions, including completion of
pain intensity rating scales.

- Leg pain radiating to or below the knee in a dermatomal pattern, diagnosed as being
due to sciatica or lumbar or lumbosacral radiculopathy, the onset of which occurred 2
to 12 weeks prior to initiation of study treatment.

- Leg pain severity on a screening Categorical Pain Intensity Rating (for the prior 24
hour period) of at least 4, using an 11-point categorical pain intensity scale with 0
= no pain and 10 = worst pain imaginable.

- Leg pain on a screening Categorical Pain Intensity Rating rated as more severe than
back pain.

- Positive straight leg raising (SLR) test as defined in Appendix B of this protocol.

- Subjects who are compliant in maintaining a Pain Diary between screening and baseline
visits, and who record a 24-hour average Categorical Pain Intensity Rating score of
at least 4 or greater on at least 3 days during the week prior to baseline visit.

- Subject who can maintain stable pharmacologic treatments for sciatica symptoms taken
prior to dosing including analgesics, anti-inflammatory medications (e.g. NSAIDS),
antidepressants, anticonvulsants, anxiolytics, or muscle relaxants. Subjects must be
on stable doses of such medications for 2 weeks prior to the baseline visit, and
maintained on the same doses throughout the study. Medications taken on an as-needed
basis are permitted, and subjects will be asked to record daily usage of such
medications in the subject diary.

- Subjects who at screening are receiving adjunctive analgesic therapy such as
acupuncture or biofeedback should either discontinue it or establish a schedule of
treatments that will remain consistent for 2 weeks prior to the baseline visit, and
throughout the study.

- Subject with screening laboratory values within normal limits, or if abnormal must be
considered not clinically significant and in the opinion of the Investigator not to
place the subjects at risk.

- If female, must be post-menopausal, surgically sterile, not currently pregnant
(verified by a screening pregnancy test) or nursing, and using a reliable
contraception method such as intrauterine device (IUD), hormonal birth control pills,
or double barrier method (male condom, female condom or diaphragm with spermicidal
jelly).

- If male, must agree to use double-barrier methods of contraception.

Exclusion Criteria:

- History of peripheral neuropathy or any other pain conditions with pain intensity
equal to or greater than the pain associated with sciatica.

- Motor loss in a muscle corresponding to the affected dermatome graded as more than
“trace”.

- History of cauda equina syndrome, symptomatic scoliosis, spondylolisthesis
(degenerative or isthmic), ankylosing spondylitis, rheumatoid arthritis or other
inflammatory arthropathies. Degenerative arthritis is allowed.

- History of hepatic, cardiovascular, renal, gastrointestinal, hematological,
neurological, endocrine (including diabetes), metabolic, pulmonary, immunological
(including HIV infection) or psychiatric disease that in the opinion of the
Investigator would pose a significant safety risk for a subject exposed to an
investigational compound such as REN-1654.

- History of the following ophthalmic disorders based upon general medical review at
the screening visit. Subjects will further undergo a screening ophthalmologic
assessment. Should any of the following be identified at the screening ophthalmologic
examination, the subject will be excluded from the study.

- Symptomatic cataract, resulting in any visual impairment (if a subject has been
diagnosed with cataract to a degree that the cataract interferes with daily
living and/or regarding which an ophthalmologist has recommended cataract
surgery);

- Other vision-impairing disorders (if a subject is aware of any eye disorder that
has impaired vision, such as age-related macular degeneration, lazy eye
(amblyopia), double vision, or any optic nerve inflammation; presbyopia and
other non-pathological visual acuity deficits are not exclusionary);

- Glaucoma or history of ocular hypertension (intraocular pressures greater than
21 mmHg).

- Cognitive or psychiatric disorders that may diminish compliance with study
procedures, including maintenance of a daily pain diary and accurate dosing of study
medication.

- Subjects who, at time of enrollment, have requested for or been advised by their
physicians to receive local, regional, or spinal (articular, epidural, intrathecal or
nerve root block) injections of medications for pain treatment or surgical
intervention for their sciatica symptoms.

- Although subjects who report work-related injuries will be allowed to enroll,
subjects will be excluded if they are involved in litigation related to the current
episode of sciatica.

- Subjects with a screening creatinine laboratory value of ≥ 2.0 mg/dL.

- Screening liver enzyme results greater than the upper limit of the normal range

- Use of chemotherapy agents or history of cancer, other than basal cell carcinoma and
squamous cell carcinoma, within five years prior to the screening visit.

- History of drug or alcohol abuse within one year prior to screening.

- Use within 2 weeks before start of study investigational compound dosing at baseline
and through the end of the study of any investigational compound, any epidural,
intrathecal, or nerve root block agent, corticosteroids, etanercept or other
anti-TNF-α agent, topical anesthetics, or topical analgesics .

- Previous participation in another REN-1654 study.