Characterizing Chronic Pain Phenotypes in Multiple Sclerosis

A Nationwide Survey Study

Anna L. Kratz; Daniel Whibley; Kevin N. Alschuler; Dawn M. Ehde; David A. Williams; Daniel J. Clauw; Tiffany J. Braley

Pain. 2021;162(5):1426-1433.

Conclusion

Results suggest that people with chronic pain and MS most commonly experience pain that has characteristics of nociceptive mechanisms or a mixed pain state, which can be described as a combination of nociceptive, nociplastic, and/or neuropathic pain characteristics. Pain that can be described as having purely neuropathic characteristics was relatively rare. This work highlights the need to assess pain phenotype in persons with chronic pain and MS to move toward a precision model of pain management in MS.

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Acknowledgements
The National Multiple Sclerosis Society (NMSS) provided participant recruitment support by distributing study advertisements through their email listserv. The Michigan Institute for Clinical and Health Research (MICHR: NIH award number UL1TR002240) provided participant recruitment support through the UMHealthResearch.org web site. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors thank Shubhangi Kulkarni, MS, for her contribution in coordinating this study and collecting these data.

Table 1. Sample descriptive statistics (N = 842).
Sex N (%)
Male	168 (20.0%)
Female	674 (80.0%)
Gender N (%)
Male	168 (20.0%)
Female	672 (79.8%)
Transgender	1 (0.1%)
Gender variant/nonconforming	1 (0.1%)
Race N (%)
White	768 (91.2%)
Black or African American	43 (5.1%)
American Indian or Alaska Native	4 (0.4%)
Asian	6 (0.7%)
Native Hawaiian or other Pacific Islander	1 (0.1%)
Bi/multi-racial	11 (1.3%)
MS type N (%)
Relapsing remitting	561 (66.6%)
Secondary progressive	137 (16.3%)
Primary progressive	78 (9.3%)
Progressive relapsing	19 (2.3%)
Not sure	47 (5.6%)
Time since MS diagnosis N (%)
<1 y	50 (5.9%)
1–5 y	183 (21.7%)
6–10 y	164 (19.5%)
11–15 y	147 (17.5%)
16–20 y	125 (14.8%)
>20 y	173 (20.5%)

Table 2. Comparison of frequency of chronic overlapping pain conditions by pain subtype.
	Full sample	Nociceptive type	Neuropathic type	Nociplastic type	Mixed type	χ²
Migraine headache	39.8% (N = 842)	33.2% (N = 341)	39.6% (N = 79)	58.2% (N = 196)	67.2% (N = 226)	χ²(3, 841) = 55.97, P <0.001
TMD	3.2% (N = 840)	0.6% (N = 341)	1.3% (N = 78)	3.6% (N = 196)	28.2% (N = 225)	χ²(3, 840) = 22.22, P <0.001
Chronic pelvic pain	23.0% (N = 837)	13.2% (N = 340)	9.0% (N = 78)	27.2% (N = 195)	39.7% (N = 224)	χ²(3, 837) = 63.94, P <0.001

Table 3. Differences by pain subtype in reported use of pain medications within the past month and related level of perceived pain relief on 0–10 numerical rating scale.
	Nociceptive type	Neuropathic type	Nociplastic type	Mixed type	Group comparison statistic
Cannabinoids	17.9% (N = 341)	20.3% (N = 79)	28.6% (N = 196)	30.5% (N = 226)	χ²(3, 842) = 15.13, P = 0.002
Mean (SD) pain relief	5.87 (2.34)_A,B	5.21 (2.67)_A	6.39 (1.93)_A,B	6.75 (2.02) _B	F(3,237) = 3.75, P = 0.01
NSAIDs	71.4% (N = 304)	70.3% (N = 74)	80.0% (N = 185)	69.4% (N = 206)	χ²(3, 763) = 20.85, P <0.001
Mean (SD) pain relief	5.88 (2.45)_A	4.98 (2.77)_{A, B, C}	4.89 (2.40)_B	4.16 (2.14)_C	F(3,556) = 15.45, P < 0.001
Opioids	11.5% (N = 304)	13.9% (N = 72)	19.5% (N = 185)	28.2% (N = 206)	χ²(3, 767) = 24.02, P <0.001
Mean (SD) pain relief	7.23 (1.52)	7.80 (1.32)	7.00 (1.84)	6.71 (1.96)	F(3,139) = 1.38, P = 0.25
Anticonvulsants	25.0% (N = 304)	45.8% (N = 72)	38.9% (N = 185)	44.7% (N = 206)	χ²(3, 767) = 26.45, P <0.001
Mean (SD) pain relief	5.99 (2.83)	5.79 (2.49)	5.67 (2.33)	5.24 (2.47)	F(3,271) = 1.25, P = 0.29
SNRIs	10.6% (N = 303)	8.3% (N = 72)	17.9% (N = 184)	22.5% (N = 204)	χ²(3, 763) = 17.17, P <0.001
Mean (SD) pain relief	5.32 (2.49)	4.83 (2.99)	4.18 (2.57)	4.43 (2.99)	F(3,115) = 1.04, P = 0.38
SSRIs	16.8% (N = 303)	11.1% (N = 72)	28.3% (N = 184)	23.5% (N = 204)	χ²(3, 763) = 14.12, P = 0.003
Mean (SD) pain relief	2.82 (3.39)	3.43 (3.78)	2.06 (2.84)	3.21 (2.98)	F(3,154) = 1.30, P = 0.28
Antispasmodics	30.7% (N = 303)	33.3% (N = 72)	44.0% (N = 184)	52.9% (N = 204)	χ²(3, 763) = 27.72, P <0.001
Mean (SD) pain relief	5.88 (2.26)	5.71 (2.91)	5.63 (2.29)	5.57 (2.15)	F(3,304) = 0.33, P = 0.80
Steroids	3.0% (N = 303)	11.1% (N = 72)	8.2% (N = 184)`	11.3% (N = 203)	χ²(3, 762) = 15.16, P = 0.002
Mean (SD) pain relief	5.78 (3.27)	5.88 (2.85)	5.33 (2.96)	5.78 (2.94)	F(3,54) = 0.09, P = 0.97
Benzodiazepines	11.6% (N = 303)	11.1% (N = 72)	18.5% (N = 184)	24.0% (N = 204)	χ²(3, 763) = 15.79, P = 0.001
Mean (SD) pain relief	4.31 (3.24)	6.63 (2.33)	3.79 (3.17)	4.67 (2.66)	F(3,125) = 2.11, P = 0.10

A, B, C, values with different subscripts indicate significant pairwise mean differences; NSAID, nonsteroidal anti-inflammatory drug; SNRI, serotonin-norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor.