How chronic pain syndromes and dry eye are correlated

Take-home message: Patients with chronic pain syndromes report worse dye eye symptoms and ocular and non-ocular pain scores, which might indicate the presence of a central pain disorder as an underlying mechanism in both conditions.

Reviewed by Anat Galor, MD, MSPH, and Roy C. Levitt, MD

Miami-There appears to be an association between chronic pain syndromes, mental health, and dry eye, which, according to the researchers who identified this link, might indicate a central pain disorder.

If this is the case, a new approach is needed for diagnosis and treatment of these patients to improve patient outcomes.

In their recent publication in The Journal of Pain (2015; Dec 1.epub), investigators led by Anat Galor, MD, MSPH, explained that recent research has shown “that dry eye susceptibility and other chronic pain syndromes such as chronic widespread pain, irritable bowel syndrome, and pelvic pain, might share common heritable factors.”

In their previous studies, this group from the Miami VAMC and Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, where Dr. Galor is associate professor of clinical ophthalmology, found that eye pain in many patients with dry eye closely resembled that of other chronic pain syndromes, such as spontaneous burning pain, hyperalgesia, and allodynia (which in the eye manifest as wind- and light-evoked pain).

These specific eye pain symptoms are associated with a more severe and chronic dry eye course that is less responsive to topical therapy with artificial tears.

Because of this, Dr. Galor and senior investigator, Roy C. Levitt, MD, a neuroanesthesiologist and pain specialist, speculated that these patients might have a different dry eye phenotype in contrast to patients with fewer chronic pain syndromes. Dr. Levitt is professor and vice chairman, Translational Research and Academic Affairs, Department of Anesthesiology, Perioperative Medicine and Pain Management, University of Miami Miller School of Medicine, Miami.

Drs. Galor and Levitt drew their study population from the Miami Veterans Affairs Hospital. The 154 study patients all had dry eye symptoms (a score on the Dry Eye Questionnaire 5 [DEQ5] of 6 or higher and normal eyelid and corneal anatomy).

Study

The patients were questioned about chronic pain that lasted for three or more months and included arthritis, burn pain, headaches, diabetic neuropathy, tendonitis, central pain syndrome, muscular pain, complex regional pain syndrome and/or causalgia, back pain, cancer pain, trigeminal neuralgia, sciatica, shingles, surgical pain, temporomandibular pain, and fibromyalgia.

Patients were divided into two groups using cluster analyses:

• cluster group 1, which was comprised of 57 patients with fewer chronic pain syndromes (mean, 2.5); and

• cluster group 2, comprised of 97 patients with more chronic pains syndromes (mean, 6.2).

All patients underwent analyses of the tear film that included determination of the tear osmolarity and tear film break-up time, corneal staining, use of Schirmer strips, and meibomian gland assessment.

Patients completed questionnaires to quantify the severity and characteristics of ocular and non-ocular pain, mental health, and quality-of-life. Non-ocular pain was assessed by the numerical rating scale. Dry eye symptoms were assessed by the DEQ5 and Ocular Surface Disease Index and eye specific pain was assessed by the numerical rating scale, Neuropathic Pain Symptom Inventory (modified for the eye) and McGill Short Form.

The main outcome measures of the study were the frequency and severity of dry eye symptoms, mental health indices, and quality-of-life parameters between patients with few chronic pain syndromes and those with more chronic pain syndromes.

Outcomes

The authors reported that in addition to worse non-ocular pain complaints and higher post-traumatic stress disorder and depression scores (p < 0.01), they found that the patients in the group with more chronic pain syndromes had more severe neuropathic-type dry eye symptoms (burning, wind- and light-evoked pain, etc.) compared with the patients with fewer chronic pain syndromes, including worse ocular pain that was assessed using the multiple pain scales (p < 0.05), with similar objective corneal dry eye signs.

The investigators also reported that psychiatric and quality-of-life measurements indicated that there were significantly worse disease scores in the patients with high chronic pain syndromes compared with the patients with low chronic pain syndromes. Specifically, they showed that the former group had higher post-traumatic stress disorder scores (PTSD) on the PTSD checklist-Military Version, higher depression scores on the Patient Health Questionnaire 9, and lower Short Form-12 physical and mental composite scores compared with the other group.

The authors speculated that an underlying central disorder of pain processing might explain the group of patients with dry eye and a higher number of chronic pain syndromes. Those patients consistently reported more neuropathic ocular pain and more severe symptoms than patients with the so-called traditional dry eye.

Notably, the differences in severity occur without difference in the corneal pathologies, which suggested the presence of a non-ocular or systemic disorder.

The mechanisms of the central disorder have not been elucidated, but numerous studies have suggested these chronic overlapping pain syndromes are “characterized by central nervous system neuroplasticity which results in increased responsiveness of nociceptive neurons and altered descending pain modulation….” such as those described in this study, as well as numerous others that include-but are not limited to-osteoarthritis, burn pain, headache, diabetic neuropathy, and muscle pain, according to the authors.

“In these patients, whose high rate of manifestation of related [chronic pain syndromes] suggests a systemic disorder, perhaps with central sensitization as the underlying mechanism, it appears that their ocular symptoms are but another peripheral manifestation of their central disease,” the investigators concluded. “This is further supported by the greater magnitude of ocular and non-ocular pain reported by the patients in high [chronic pain syndromes] group in this study.”

Anat Galor, MD, MSPH

E: agalor@med.miami.edu

Roy C. Levitt, MD

E: rlevitt@med.miami.edu

Dr. Galor and Levitt have no financial interest in the subject matter.