Elizabeth R. Felix

Pain after Spinal Cord Injury: A Review of Classification, Treatment Approaches, and Treatment Assessment

Pain is a prevalent consequence of spinal cord injury (SCI) that can persist for years after the injury and can have a significant impact on physical and emotional function and quality of life. There are a variety of types of pain that may develop after a SCI, including those of primarily nociceptive origin and those of primarily neuropathic origin. Recommendations for diagnostic and treatment strategies have been varied in part because of the lack of a universal classification system and in part because of the biopsychosocial nature of pain. The most recent taxonomy for pain after SCI is described herein. Pain‐management strategies, including pharmacological, interventional, and psychological treatments, also are described. For neuropathic pain in SCI, anticonvulsant agents and tricyclic antidepressants often are tried, but these treatments have had limited success in many patients, and alternative interventions (eg, massage therapy, acupuncture, meditation) often are just as successful. Treatment of nociceptive pain after SCI often includes nonsteroidal antiinflammatory agents and acetaminophen, but correction of underlying etiologies and behavior adjustments also should be implemented if possible. An overview of self‐report pain questionnaires and scales is also presented to provide the clinician and researcher with a set of tools to evaluate the efficacy of pain interventions.

Dry eye symptom severity and persistence are associated with symptoms of neuropathic pain.

Objective Studies of patients with non-ocular pain suggest that it is therapeutically useful to identify those with features of neuropathic pain. No data is available, however, on whether this approach has similar utility in dry eye. The purpose of this study was to determine whether severity and persistence of dry eye symptoms associate with self-reported symptoms of neuropathic ocular pain (NOP). Methods Design: Cohort study. Participants/setting: 102 men seen in the Miami Veterans Affairs eye clinic. A baseline evaluation was performed consisting of the dry eye questionnaire 5 (DEQ5) and ocular surface evaluation. Patients were contacted ≥2 years later to repeat the DEQ5 and complete questionnaires that further characterised their eye pain. Main outcome measure: The relationship between dry eye symptom severity and persistence (DEQ5) and additional measures of ocular pain (NOP). Results Of 102 patients with variable dry eye symptoms, 70 reported at least mild symptoms on both encounters (DEQ5≥6). Fifty-four of 70 (77%) reported ≥1 NOP feature, and the number of NOP features correlated moderately with dry eye symptoms at both encounters (r=0.31–0.46, p<0.01). Patients with any symptom of NOP had higher dry eye symptom scores at both encounters (p<0.05), but similar ocular surface parameters. Hypersensitivity to wind and photoallodynia were associated with having mild or greater symptoms on both encounters (OR 3.4, 95% CI 1.2 to 10.0, p=0.02; OR 15.6, 95% CI 2.0 to 123, p=0.009, respectively). Conclusions NOP features are common in patients with symptomatic dry eye and these features correlate with symptom severity and persistence.

Dry eye symptoms align more closely to non-ocular conditions than to tear film parameters

Objective To evaluate the relationship between dry eye symptoms, non-ocular conditions and tear film parameters. Methods Design: Cross-sectional study. Participants/setting: The study population consisted of patients who were seen in the Miami Veterans Affairs eye clinic. Patients filled out standardised questionnaires assessing dry eye symptoms (dry eye questionnaire 5 (DEQ5) and ocular surface disease index (OSDI)), non-ocular pain, depression and post-traumatic stress disorder (PTSD), and also underwent measurement of tear film parameters. Main outcome measures: Correlations between dry eye symptoms and non-ocular conditions as compared with tear film parameters. Results 136 patients with a mean age of 65 (SD 11) years participated in the study. All correlations between the dry eye questionnaire scores (DEQ5 and OSDI) and (A) self-reported non-ocular pain measures (numerical rating scale and pain history), (B) depression and (C) PTSD were significant and moderate in strength (Pearsons coefficient 0.24 to 0.60, p<0.01 for all). All correlations between the dry eye questionnaires and tear film measures were weak (Pearsons coefficient −0.10 to 0.18) and most were not significant. Multivariable linear regression analyses revealed that PTSD and non-ocular pain more closely associated with dry eye symptoms than did tear film parameters. Specifically, non-ocular pain and PTSD accounted for approximately 36% of the variability in DEQ5 scores (R=0.60) and approximately 40% of variability in OSDI scores (R=0.64). Of note, none of the tear parameters remained significantly associated with dry eye symptoms in either model. Conclusions Dry eye symptoms more closely align to non-ocular pain, depression and PTSD than to tear film parameters.

Pain Symptom Profiles in Persons with Spinal Cord Injury

OBJECTIVE Persistent pain is a common consequence of spinal cord injury. A patient-specific assessment that combines both the identification of pain symptoms and psychosocial factors is needed for a tailored treatment approach. The aim of the study was to define pain symptom profiles and to determine their relationship with psychosocial factors in persons with spinal cord injury. DESIGN Face-to-face interview and examination. SETTING VA Medical Center and Miami Project to Cure Paralysis, Miami, Florida. PATIENTS Persons with spinal cord injury (135 men and 21 women) provided detailed descriptions of 330 neuropathic pains. OUTCOME MEASURES The American Spinal Injury Impairment Scale, pain history and measures of pain interference, life satisfaction, locus of control, social support and depression. RESULTS The exploratory factor analyses and regression analyses revealed three distinct symptom profiles: 1) aching, throbbing pain, aggravated by cold weather and constipation predicted by a combination of chance locus of control and lower levels of life satisfaction; 2) stabbing, penetrating, and constant pain of high intensity predicted by a combination of pain interference, localized pain, powerful others locus of control and depressed mood; and 3) burning, electric, and stinging pain aggravated by touch and muscle spasms predicted by pain interference. CONCLUSIONS Although these results need to be replicated in other spinal cord injury samples, our findings suggest that pain symptom profiles may be a useful way to further characterize pain in a comprehensive assessment strategy.

Incomplete response to artificial tears is associated with features of neuropathic ocular pain

Aims Artificial tears are first-line therapy for patients with dry eye symptoms. It is not known, however, which patient factors associate with a positive response to therapy. The purpose of this study was to evaluate whether certain ocular and systemic findings are associated with a differential subjective response to artificial tears. Methods Cross-sectional study of 118 individuals reporting artificial tears use (hypromellose 0.4%) to treat dry eye-associated ocular pain. An evaluation was performed to assess dry eye symptoms (via the dry eye questionnaire 5 and ocular surface disease index), ocular and systemic (non-ocular) pain complaints and ocular signs (tear osmolarity, tear breakup time, corneal staining, Schirmer testing with anaesthesia, and eyelid and meibomian gland assessment). The main outcome measures were factors associated with differential subjective response to artificial tears. Results By self-report, 23 patients reported no improvement, 73 partial improvement and 22 complete improvement in ocular pain with artificial tears. Patients who reported no or partial improvement in pain with artificial tears reported higher levels of hot-burning ocular pain and sensitivity to wind compared with those with complete improvement. Patients were also asked to rate the intensity of systemic pain elsewhere in the body (other than the eye). Patients who reported no or incomplete improvement with artificial tears had higher systemic pain scores compared with those with complete improvement. Conclusions Both ocular and systemic (non-ocular) pain complaints are associated with a differential subjective response to artificial tears.

Corneal Mechanical Thresholds Negatively Associate With Dry Eye and Ocular Pain Symptoms.

Purpose To examine associations between corneal mechanical thresholds and metrics of dry eye. Methods This was a cross-sectional study of individuals seen in the Miami Veterans Affairs eye clinic. The evaluation consisted of questionnaires regarding dry eye symptoms and ocular pain, corneal mechanical detection and pain thresholds, and a comprehensive ocular surface examination. The main outcome measures were correlations between corneal thresholds and signs and symptoms of dry eye and ocular pain. Results A total of 129 subjects participated in the study (mean age 64 ± 10 years). Mechanical detection and pain thresholds on the cornea correlated with age (Spearmans ρ = 0.26, 0.23, respectively; both P < 0.05), implying decreased corneal sensitivity with age. Dry eye symptom severity scores and Neuropathic Pain Symptom Inventory (modified for the eye) scores negatively correlated with corneal detection and pain thresholds (range, r = −0.13 to −0.27, P < 0.05 for values between −0.18 and −0.27), suggesting increased corneal sensitivity in those with more severe ocular complaints. Ocular signs, on the other hand, correlated poorly and nonsignificantly with mechanical detection and pain thresholds on the cornea. A multivariable linear regression model found that both posttraumatic stress disorder (PTSD) score (β = 0.21, SE = 0.03) and corneal pain threshold (β = −0.03, SE = 0.01) were significantly associated with self-reported evoked eye pain (pain to wind, light, temperature) and explained approximately 32% of measurement variability (R = 0.57). Conclusions Mechanical detection and pain thresholds measured on the cornea are correlated with dry eye symptoms and ocular pain. This suggests hypersensitivity within the corneal somatosensory pathways in patients with greater dry eye and ocular pain complaints.

Dry Eye Profiles in Patients with a Positive Elevated Surface Matrix Metalloproteinase 9 Point-of-Care Test Versus Negative Patients

PURPOSE To compare dry eye (DE) symptoms and signs in subjects who tested positive versus those who tested negative for ocular surface matrix metalloproteinase 9 (MMP-9) using the InflammaDry point-of-care test (RPS, Sarasota, FL). METHODS In this cross-sectional study, individuals seen in the Miami Veterans Affairs eye clinic with DE symptoms, as evidenced by DE questionnaire 5 (DEQ5) ≥6, were given standardized questionnaires to assess DE symptoms and ocular and non-ocular pain complaints. Also, a complete evaluation was conducted to measure ocular surface signs of DE. MMP-9 testing was performed using the InflammaDry once in each eye, per the manufacturers instructions. The main outcome measure was a comparison of DE symptoms and signs in MMP-9 positive versus negative subjects. RESULTS Of 128 subjects, 50 (39%) were positive for MMP-9 for InflammaDry testing in either eye. No statistically significant differences in mental health indices, DE symptoms, or ocular surface signs were seen in subjects based on MMP-9 status. CONCLUSION In our population, there was no difference in the DE profile by both symptoms and signs between those testing positive versus negative for MMP-9 on the ocular surface. This suggests that clinical exam alone cannot predict patients with clinically significant inflammation.

Multidimensional Neuropathic Pain Phenotypes after Spinal Cord Injury

Identifying clinical neuropathic pain phenotypes is a first step to better understand the underlying pain mechanisms after spinal cord injury (SCI). The primary purpose of the present study was to characterize multidimensional neuropathic pain phenotypes based on quantitative sensory testing (QST), pain intensity, and utilization of catastrophizing coping strategies. Thermal perception, thermal pain, and vibratory perception thresholds were assessed above and below the level of injury (LOI) in 101 persons with SCI and neuropathic pain, 18 persons with SCI and no neuropathic pain, and 50 able-bodied, pain-free controls. Cluster analysis of QST z-scores below the LOI, pain intensity ratings, and the Coping Strategies Questionnaire (CSQ) catastrophizing subscale scores in subjects with neuropathic pain resulted in two phenotypes: severe neuropathic pain (SNP) with greater pain intensity (7.39 ± 1.57) and thermal and vibratory sensitivity compared with the moderate neuropathic pain (MNP; 5.40 ± 1.43). A factor analysis including all CSQ subscales, the Neuropathic Pain Symptom Inventory (NPSI) total score, and thermal pain sensitivity above and below the LOI resulted in three factors: (1) adaptive pain coping including increasing activities, diverting attention, and reinterpreting pain sensations; (2) catastrophizing, neuropathic pain, and thermal sensitivity including greater NPSI total score, thermal pain sensitivity below the LOI, and catastrophizing; and (3) general pain sensitivity including greater thermal pain sensitivity above the LOI and lower catastrophizing. Our results suggest that neuropathic pain symptom severity post-SCI is significantly associated with residual spinothalamic tract function below the LOI and catastrophizing pain coping.

Assessment of Somatosensory Function in Patients With Idiopathic Dry Eye Symptoms

Importance Somatosensory dysfunction likely underlies dry eye (DE) symptoms in many individuals yet remains an understudied component of the disease. Its presence has important diagnostic and therapeutic implications. Objective To assess the integrity of nociceptive system processes in persons with DE and ocular pain using quantitative sensory testing (QST) techniques applied at a site remote from the eye. Design, Setting, and Participants A cross-sectional study conducted at Miami Veterans Affairs Hospital included 118 individuals with a wide variety of DE symptoms and signs. The study was conducted from October 31, 2013, to January 28, 2016. Interventions Individuals completed questionnaires regarding ocular symptoms (5-Item Dry Eye Questionnaire [DEQ5], Ocular Surface Disease Index [OSDI], and Neuropathic Pain Symptom Inventory modified for the eye [NPSI-E]), psychological status, and medication use and underwent an ocular surface examination. The QST metrics included measures of vibratory and thermal thresholds and cold and hot pain temporal summation (surrogate measures of central sensitization) on the forearm. Main Outcomes and Measures Correlations among DE and ocular pain symptom severity with QST metrics measured on the forearm. The OSDI score ranges from 0 to 100, with 100 indicating the most severe DE symptoms. The DEQ5 score ranges from 0 to 22, with the highest score indicating the most severe symptoms, and the NPSI-E score ranges from 0 to 100, with the highest score indicating the most severe symptoms. Psychological state was measured with the 9-item Patient Health Questionnaire, the PTSD Checklist-Military Version for PTSD, and the Symptom Checklist-90 for anxiety. Results Of the 118 patients who participated in the study, 105 (88.9%) were men (mean [SD] age, 60 [10] years), and a mean of 41% had PTSD, 10% depression, and 0.93% anxiety. Using stepwise linear regression analyses, significant associations were identified between overall DE symptom severity and posttraumatic stress disorder scores and tear breakup time (DEQ5 model: R = 0.54; OSDI model: R = 0.61, P < .001). All other variables (ie, demographics, comorbidities, medications, tear film factors, and QST metrics) dropped out of these models. When specifically considering neuropathic-like qualities of DE pain, however, anxiety and hot pain temporal summation at the forearm explained 17% of the variability in ocular burning (R = 0.41; P < .001), and PTSD score, tear breakup time, and hot pain temporal summation at the forearm explained 25% of the variability in sensitivity to wind (R = 0.50; P < .001) and 30% of the variability in total NPSI-E scores (R = 0.55; P < .001). Conclusions and Relevance Our findings demonstrate that neuropathic-like DE pain symptom severity correlates with quantitative measures of pain sensitivity at a site remote from the eye. This result provides additional evidence that DE symptoms are not only manifestations of a local disorder but also involve somatosensory dysfunction beyond the trigeminal system.

Resilience Following Traumatic Brain Injury: A Traumatic Brain Injury Model Systems Study

OBJECTIVE To examine resilience at 3 months after traumatic brain injury (TBI). DESIGN Cross-sectional analysis of an ongoing observational cohort. SETTING Five inpatient rehabilitation centers, with 3-month follow-up conducted primarily by telephone. PARTICIPANTS Persons with TBI (N=160) enrolled in the resilience module of the TBI Model System study with 3-month follow-up completed. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURE Connor-Davidson Resilience Scale. RESULTS Resilience scores were lower than those of the general population. A multivariable regression model, adjusting for other predictors, showed that higher education, absence of preinjury substance abuse, and less anxiety at follow-up were significantly related to greater resilience. CONCLUSIONS Analysis suggests that lack of resilience may be an issue for some individuals after moderate to severe TBI. Identifying persons most likely at risk for low resilience may be useful in planning clinical interventions.