Economic and humanistic burden of post-trauma and post-surgical neuropathic pain among adults in the United States

Figures & data

Table 1 Validated patient-reported outcome measures included in the subject questionnaire

Patient-reported outcome measure	Description
Brief Pain Inventory-Short Form (BPI-SF)	An 11-item measure of pain severity (4 items: worst, least, average, current; 0–10 scale [higher scores indicate more severe pain]) and pain interference with function (7 items; 0–10 scale [higher scores indicate more interference])^Citation33
12-item Short-Form Health Survey (SF-12) (1-week recall)	A 12-item measure of health status with 8 domains and physical and mental component scores (0–100 scale [higher scores indicate better outcomes])^Citation34
EuroQol Five-Dimensions (EQ-5D), three-levels	A 5-item general health status and utility measure (−0.11 to 1.00 scale [higher scores indicate better outcomes])^Citation35
Medical Outcomes Study Sleep Scale (MOS-SS)	A 12-item measure of sleep outcomes (9 items make up the Sleep Problems Index; 0–100 scale [higher scores indicate more sleep problems])^Citation26
Hospital Anxiety and Depression Scale (HADS)	A 14-item measure of anxiety (7 items; 0–21 scale [scores 0–7 represent “normal,” 8–10 “mild,” 11–14 “moderate,” and 15–21 “severe” levels of anxiety]) and depression (7 items; 0–21 scale [scores 0–7 represent “normal,” 8–10 “mild,” 11–14 “moderate,” and 15–21 “severe” levels of depression])^Citation36,Citation37
Work Productivity and Activity Impairment (WPAI) due to PTPS NeP	A 6-item measure used to quantify absenteeism, presenteeism and daily activity impairment customized to PTPS NeP (scores expressed as impairment percentages [higher scores indicate more productivity loss and greater impairment])^Citation38

Abbreviations: PTPS, post-traumatic/post-surgical; NeP, neuropathic pain.

Figure 1 PTPS NeP subjects reported a variety of comorbid conditions.^a

Notes: ^aScores on the BPI-SF Pain Severity Index were used to classify average pain severity. Three subjects did not respond to all required items needed to calculate a BPI-SF average pain severity score, and thus were not included in any analysis by pain severity category; **statistically significant differences were observed across pain severity levels at the P < 0.05 level as follows: depressive symptoms (P = 0.0205), restless leg syndrome (P = 0.0293), and chronic fatigue syndrome (P = 0.0025).
Abbreviations: PTPS, post-traumatic/post-surgical; NeP, neuropathic pain; BPI-SF, Brief Pain Inventory-Short Form.

Table 2 Demographic and clinical characteristics, overall, by average pain severity

Characteristic	Overall (n = 100)	Mild (0–3) (n = 14)	Moderate (4–6) (n = 48)	Severe (7–10) (n = 35)	P-value*
Age, years					0.0037**
Mean (SD)	54.9 (12.87)	63.6 (11.09)	56.2 (12.49)	49.4 (11.75)
Gender, n (%)					0.7263
Female	53 (53.0)	7 (50.0)	23 (47.9)	20 (57.1)
Race, n (%)					0.0029**
Missing	2 (2.0)	0 (0.0)	0 (0.0)	2 (5.7)
American Indian or Alaska Native	3 (3.0)	0 (0.0)	1 (2.1)	2 (5.7)
Asian	1 (1.0)	0 (0.0)	0 (0.0)	1 (2.9)
Black or African American	3 (3.0)	0 (0.0)	0 (0.0)	3 (8.6)
Native Hawaiian or Other Pacific Islander	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
White	85 (85.0)	14 (100.0)	47 (97.9)	21 (60.0)
Multiracial	3 (3.0)	0 (0.0)	0 (0.0)	3 (8.6)
Other	3 (3.0)	0 (0.0)	0 (0.0)	3 (8.6)
Education level, n (%)					0.3824
Missing	4 (4.0)	0 (0.0)	1 (2.1)	3 (8.6)
Up to high school/GED	30 (30.0)	3 (21.4)	13 (27.1)	13 (37.1)
Beyond high school	66 (66.0)	11 (78.6)	34 (70.8)	19 (54.3)
Employment status, n (%)					0.0002**
Employed for pay	22 (22.0)	4 (28.6)	13 (27.1)	5 (14.3)
Disableda	48 (48.0)	1 (7.1)	23 (47.9)	22 (62.9)
Retired	18 (18.0)	7 (50.0)	9 (18.8)	1 (2.9)
Unemployed	8 (8.0)	1 (7.1)	3 (6.3)	4 (11.4)
Other	4 (4.0)	1 (7.1)	0 (0.0)	3 (8.6)
BPI-SF Pain Severity Index					NA
Mean (SD)	5.6 (2.09)	2.0 (1.08)	5.2 (0.80)	7.7 (0.98)
NeP prescription coverage, n (%)					0.0845
Missing	1 (1.0)	0 (0.0)	1 (2.1)	0 (0.0)
No	14 (14.0)	1 (7.1)	4 (8.3)	9 (25.7)
Yes	85 (85.0)	13 (92.9)	43 (89.6)	26 (74.3)
Time since trauma/surgery, n (%)					0.4076
6 months to 1 year	3 (3.0)	0 (0.0)	1 (2.1)	1 (2.9)
1 to 2 years	7 (7.0)	0 (0.0)	6 (12.5)	1 (2.9)
>2 years	90 (90.0)	14 (100.0)	41 (85.4)	33 (94.3)
Time since NeP diagnosis, monthsb					0.9083
Mean (SD)	107.8 (85.59)	103.5 (80.37)	116.4 (99.37)	98.8 (67.21)
Time since first experienced NeP symptoms, monthsc					0.2786
Mean (SD)	117.5 (98.88)	87.0 (78.70)	128.9 (101.39)	115.4 (104.49)

Notes:

* P-values are from the Kruskal–Wallis test for continuous variables and the Fisher’s exact test for the categorical variables; mild versus moderate versus severe;

** statistically significant at the 0.05 level;

a disabled/on disability, defined as individuals granted disabled status by the US government and receiving monthly disability payments from the Social Security Administration;

b reported on the clinical case report form based on physician review of subject’s medical chart;

c reported on the subject questionnaire based on subject’s recall. Mild, moderate, and severe classification was based on the BPI-SF average pain severity score. Three subjects did not respond to all required items needed to calculate a BPI-SF average pain severity score and thus were not included in any analysis by pain severity category.

Abbreviations: n, number; SD, standard deviation; GED, general education development; BPI-SF, Brief Pain Inventory-Short Form; NA, not applicable; NeP, neuropathic pain; BPI-SF, Brief Pain Inventory-Short Form.

Figure 2 PTPS NeP subjects with more severe pain reported significantly worse physical and mental health.^a

Notes: ^aScores on the BPI-SF Pain Severity were used to classify average pain severity. Three subjects did not respond to all required items needed to calculate a BPI-SF average pain severity score and thus were not included in any analysis by pain severity category. SF-12 PCS and MCS both scored on a scale of 0–100; population norms (PCS = 49.7 and MCS = 49.5),²⁴ indicated by thick black horizontal lines. **Statistically significant differences were observed by pain severity levels at the P < 0.05 level for the PCS (P = 0.0004); ***statistically significant differences were observed by pain severity levels at the P < 0.0001 level for the MCS.
Abbreviations: PTPS, post-traumatic/post-surgical; NeP, neuropathic pain; BPI-SF, Brief Pain Inventory-Short Form; PCS, Physical Component Summary; MCS, Mental Component Summary; SF-12, Short-Form Health Survey.

Figure 3 PTPS NeP subjects with more severe pain have significantly worse general health status.^a

Notes: ^aScores on the BPI-SF Pain Severity were used to classify average pain severity. Three subjects did not respond to all required items needed to calculate a BPI-SF average pain severity score and thus were not included in any analysis by pain severity category. EQ-5D scored on a scale of 0–1.0; the population norm (0.87)²⁵ is indicated by black horizontal line. ***A statistically significant difference was observed across pain severity levels for EQ-5D health state utility: P < 0.0001.
Abbreviations: PTPS, post-traumatic/post-surgical; NeP, neuropathic pain; BPI-SF, Brief Pain Inventory-Short Form; EQ-5D, EuroQol Five-Dimensions.

Figure 4 PTPS NeP subjects with more severe pain experience, more interference with function.^a

Notes: ^aScores on the BPI-SF Pain Severity were used to classify average pain severity. Three subjects did not respond to all required items needed to calculate a BPI-SF average pain severity score and thus were not included in any analysis by pain severity category. BPI-SF Pain Severity Index scored on a 0–10 scale. ***A statistically significant difference was observed across pain severity levels for BPI-SF Pain Interference Index: P < 0.0001.
Abbreviations: PTPS, post-traumatic/post-surgical; NeP, neuropathic pain; BPI-SF, Brief Pain Inventory-Short Form.

Figure 5 PTPS NeP subjects with more severe pain reported worse sleep outcomes.^a

Notes: ^aScores on the BPI-SF Pain Severity were used to classify average pain severity. Three subjects did not respond to all required items needed to calculate a BPI-SF average pain severity score and thus were not included in any analysis by pain severity category. MOS-SS Sleep Disturbance and Sleep Problems Index are both scored on a scale from 0–100; the MOS-SS Sleep Problems Index population norm (25.8)²⁶ is indicated by a black horizontal line. ***A statistically significant difference was observed across pain severity levels for the MOS-SS Sleep Disturbance and Sleep Problems Index; both P < 0.0001.
Abbreviations: PTPS, post-traumatic/post-surgical; NeP, neuropathic pain; BPI-SF, Brief Pain Inventory-Short Form; MOS-SS, Medical Outcomes Study Sleep Scale.

Figure 6 PTPS NeP subjects with more severe pain experience, more anxiety and depression.^a

Notes: ^aScores on the BPI-SF Pain Severity were used to classify average pain severity. Three subjects did not respond to all required items needed to calculate a BPI-SF average pain severity score, and thus were not included in any analysis by pain severity category. Anxiety and depression were scored on a 0–21 scale: normal (0–7), mild (8–10), moderate (11–14), severe (15–21). The difference observed across pain severity levels for HADS Anxiety was not significant at the 0.05 significance level; P = 0.0553. ***A statistically significant difference was observed across pain severity levels for HADS depression: P < 0.0001.
Abbreviations: PTPS, post-traumatic/post-surgical; NeP, neuropathic pain; BPI-SF, Brief Pain Inventory-Short Form; HADS, Hospital Anxiety and Depression Scale.

Figure 7 Use of PTPS NeP prescription medications.

Notes: ^aFigure includes all reported classes, except miscellaneous agents, with >2% of subjects prescribed one or more medication(s) in the class; ^bopioids (all) includes strong short-acting opioids (47.0%), long-acting opioids (31.0%), and weak short-acting opioids (18.0%). Subjects may have been prescribed more than one type of opioids.
Abbreviations: PTPS, post-traumatic/post-surgical; NeP, neuropathic pain; SNRI, serotonin–norepineprhine reuptake inhibitor; NSAIDs, nonsteroidal anti-inflammatory drugs; TCAs, tricyclic antidepressants.

Table 3 Resource utilization for PTPS NeP, overall, by average pain severity

Resource use	Overall (n = 100)	Mild (0–3) (n = 14)	Moderate (4–6) (n = 48)	Severe (7–10) (n = 35)	P-value*
Medication
Prescription medications prescribed to subjecta					0.1404
Mean (SD)	2.6 (1.47)	2.1 (1.14)	2.7 (1.19)	2.8 (1.89)
Number of NeP medications prescribed to subject, n (%)					0.1141
0	3 (3.0)	0 (0.0)	1 (2.1)	2 (5.7)
1	15 (15.0)	4 (28.6)	6 (12.5)	5 (14.3)
2	36 (36.0)	8 (57.1)	15 (31.3)	11 (31.4)
3	25 (25.0)	0 (0.0)	17 (35.4)	8 (22.9)
4	10 (10.0)	1 (7.1)	4 (8.3)	4 (11.4)
5	8 (8.0)	1 (7.1)	5 (10.4)	2 (5.7)
≥6	3 (3.0)	0 (0.0)	0 (0.0)	3 (8.6)
Number of nonprescription medications usedb					0.0267**
Mean (SD)	0.9 (1.22)	0.4 (1.60)	1.0 (1.10)	1.0 (1.21)
Used nonprescription medication in the past 4 weeks, n (%)					0.0050**
No	55 (55.0)	13 (92.9)	22 (45.8)	18 (51.4)
Yes	45 (45.0)	1 (7.1)	26 (54.2)	17 (48.6)
Office visita
Physician office visits for NeP					0.0065**
Mean (SD)	5.3 (2.54)	3.4 (2.50)	5.9 (2.29)	5.0 (2.54)
Non-physician office visits for NeP					0.2333
Mean (SD)	0.2 (0.70)	0.0 (0.00)	0.1 (0.32)	0.3 (1.07)
Tests and proceduresa
Outpatient tests or procedures					0.5353
Mean (SD)	1.4 (1.77)	1.1 (1.64)	1.2 (1.66)	1.5 (1.70)
ER visits for NePa					0.6392
Yes, n (%)	2 (2.0)	0 (0.0)	2 (4.2)	0 (0.0)
Hospital outpatient visits for NePa					0.0981
Yes, n (%)	3 (3.0)	0 (0.0)	0 (0.0)	3 (8.6)
Hospitalizations for NePa					0.7322
Yes, n (%)	3 (3.0)	0 (0.0)	1 (2.1)	2 (5.7)

Notes:

* P-values are from the Kruskal–Wallis test for continuous variables and the Fisher’s exact test for the categorical variables; mild versus moderate versus severe;

** statistically significant at the 0.05 level;

a over the past 6 months;

b over the past 4 weeks. Mild, moderate, and severe classification was based on the BPI-SF average pain severity score. Three subjects did not respond to all required items needed to calculate a BPI-SF average pain severity score, and thus were not included in any analysis by pain severity category.

Abbreviations: PTPS, post-traumatic/post-surgical; NeP, neuropathic pain; n, number; SD, standard deviation; ER, emergency room; BPI-SF, Brief Pain Inventory-Short Form.

Figure 8 PTPS NeP impact on employment status.^a,**

Notes: ^aScores on the BPI-SF Pain Severity were used to classify average pain severity. Three subjects did not respond to all required items needed to calculate a BPI-SF average pain severity score, and thus were not included in any analysis by pain severity category. **A statistically significant difference was observed across pain severity levels at the 0.05 level for the impact of PTPS NeP on employment status; P = 0.0002.
Abbreviations: PTPS, post-traumatic/post-surgical; NeP, neuropathic pain; BPI-SF, Brief Pain Inventory-Short Form.

Figure 9 PTPS NeP subjects with more severe pain experienced greater losses in productivity.^a

Notes: ^aScores on the BPI-SF Pain Severity were used to classify average pain severity. Three subjects did not respond to all required items needed to calculate a BPI-SF average pain severity score and thus were not included in any analysis by pain severity category. WPAI overall work impairment among those employed, and activity impairment among both employed and unemployed scored on a 0%–100% scale. **A statistically significant difference was observed across pain severity levels at the 0.05 level for overall work impairment (P = 0.0026). ***A statistically significant difference was observed across pain severity levels at the <0.0001 level for activity impairment (P < 0.0001).
Abbreviations: PTPS, post-traumatic/post-surgical; NeP, neuropathic pain; BPI-SF, Brief Pain Inventory-Short Form; WPAI, Work Productivity and Activity Impairment.

Figure 10 Adjusted average annualized cost per PTPS NeP subject, overall and by average pain severity.^a

Notes: ^aScores on the BPI-SF Pain Severity were used to classify average pain severity as follows: 0–3 represents mild pain, 4–6 represents moderate pain, and 7–10 represents severe pain; ^baverage annualized total direct cost per subject was significantly different by pain severity (P < 0.0001). Direct costs include physician visits, other health care provider visits, prescription medications, TENS device, outpatient tests/procedures, emergency room visits, hospital outpatient visits, hospitalizations, direct medical costs to subjects, and direct nonmedical costs (child care, help with house and/or yard work, and help with activities of daily living) due to PTPS NeP. ^cAverage annualized total indirect cost per subject was significantly different by pain severity (P < 0.0001). Total indirect costs include overall work impairment, activity impairment, disability, unemployment, early retirement, and reduced work schedule due to PTPS NeP. ^dAdjusted LS mean estimates from multiple linear regression adjusted for confounding demographic and clinical variables – specifically, covariates for direct costs: ethnicity, pain severity (mild/moderate/severe only), prescription coverage, and comorbidities (headache/migraine, major depressive disorder, irritable bowel syndrome, cognitive dysfunction, chronic fatigue syndrome [overall only], sleep disturbance/insomnia, chronic low back pain, and other); and for indirect costs: age, race, pain severity, and comorbidities (major depressive disorder and irritable bowel syndrome).
Abbreviations: PTPS, post-traumatic/post-surgical; NeP, neuropathic pain; BPI-SF, Brief Pain Inventory-Short Form; TENS, transcutaneous electrical nerve stimulation; LS, least squares.

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