Effects of pain on cognitive function and mobility

Figures & data

Figure 1 Participant disposition.

Note: ^aOne subject in the placebo group had a protocol violation, completed the study, but was excluded from the mITT population; therefore, total mITT population n=20.
Abbreviations: ITT, intent-to-treat; mITT, modified intent-to-treat.

Table 1 Demographic characteristics

	Paracetamol 500 mg+ caffeine 65 mg (n=6)	Paracetamol 500 mg (n=7)	Placebo (n=8)	Overall (N=21)
Sex, n (%)
Female	4 (66.7)	5 (71.4)	5 (62.5)	14 (66.7)
Male	2 (33.3)	2 (28.6)	3 (37.5)	7 (33.3)
Race, n (%)
White	3 (50.0)	5 (71.4)	4 (50.0)	12 (57.1)
Asian	2 (33.3)	2 (28.6)	1 (12.5)	5 (23.8)
Black	1 (16.7)	0	2 (25.0)	3 (14.3)
Multiple	0	0	1 (12.5)	1 (4.8)
Age, years
Mean ± SD	27.8±4.8	30.0±9.5	40.0± 15.9	33.2± 12.3
Range	20–35	20–47	26–63	20–63
BMI, kg/m^2
Mean ± SD	22.30±2.5	23.5±2.5	24.3±3.3	23.5±2.8
Range	18.7–24.5	20.3–27.4	20.1–27.8	18.7–27.8

Abbreviation: BMI, body mass index.

Table 2 Cognitive function assessments during untreated pain state (Visit 2, pretreatment) relative to pain-free state (Visit 3), mITT population

	Paracetamol 500 mg + caffeine 65 mg (n=6)	Paracetamol 500 mg (n=7)	Placebo (n=7)
Axon Sport – Error-Adjusted Simple Reaction Time, ms^a
Pain state	n=6	n=7	n=7
Median (range)	0.48 (0.3–0.6)	0.39 (0.3–1.2)	0.44 (0.4–0.8)
Pain-free state	n=6	n=6	n=5
Median (range)	0.36 (0.3–0.6)	0.36 (0.3–0.4)	0.43 (0.4–0.6)
Change (pain vs pain-free)	n=6	n=6	n=5
Median (range)	0.05 (0.0–0.2)	0.07 (0.0–0.8)	0.06 (0.0–0.2)
P-value	0.0625	0.0313^b	0.0625
Reaction Time, ms^a
Pain state	n=6	n=7	n=7
Median (range)	407.75 (389.5–510.0)	427.00 (374.0–592.5)	418.00 (382.5–435.5)
Pain-free state	n=6	n=6	n=5
Median (range)	401.00 (384–511.5)	410.50 (392.0–468.0)	417.00 (399.5–442.0)
Change (pain vs pain-free)	n=6	n=6	n=5
Median (range)	2.00 (−17.5 to 36.0)	−1.75 (−41.0 to 170.5)	−1.00 (−6.5 to 18.5)
P-value	0.5625	0.9999	0.6875
Rapid Visual Information Processing^c
Pain state	n=6	n=7	n=7
Mean ± SD	0.91±0.037	0.95±0.056	0.91±0.056
Pain-free state	n=6	n=6	n=4
Mean ± SD	0.95±0.020	0.96±0.055	0.93±0.052
Change (pain vs pain-free)	n=6	n=6	n=4
Mean (95% CI)	−0.04 (−0.08 to −0.01)	−0.01 (−0.02 to 0.01)	−0.03 (−0.07 to 0.00)
P-value	0.0227^b	0.2785	0.0557
Attention Switching Task, ms^a
Pain state	n=6	n=7	n=7
Median (range)	62.00 (25.0–74.0)	57.50 (0.0–163.0)	85.00 (55.5–189.0)
Pain-free state	n=6	n=6	n=5
Median (range)	66.25 (18.5–75.5)	43.00 (0.0–77.0)	82.50 (40.5–193.0)
Change (pain vs pain-free)	n=6	n=6	n=5
Median (range)	−3.25 (−44.5 to 46.5)	46.25 (−22.5 to 99.5)	2.50 (−4.0 to 113.5)
P-value	0.9999	0.1563	0.3125
Spatial Working Memory^c
Pain state	n=6	n=7	n=7
Mean ± SD	35.67±30.32	37.00±29.88	58.43±20.15
Pain-free state	n=6	n=6	n=5
Mean ± SD	45.0±20.86	7.67±5.09	44.00±39.21
Change (pain vs pain-free)	n=6	n=6	n=5
Mean (95% CI)	−9.33 (−29.01 to 10.34)	25.17 (−5.35 to 55.68)	13.80 (−15.99 to 43.59)
P-value	0.2770	0.0875	0.2678
One Touch Stockings of Cambridge^c
Pain state	n=6	n=7	n=7
Mean ± SD	10.00±2.61	10.71±1.80	12.14±1.77
Pain-free state	n=6	n=6	n=5
Mean ± SD	12.67±1.75	11.17±1.47	12.40±3.05
Change (pain vs pain-free)	n=6	n=6	n=5
Mean (95% CI)	−2.67 (−5.90 to 0.56)	0.00 (−1.15 to 1.15)	−0.20 (−2.42 to 2.02)
P-value	0.0872	0.9999	0.8149

Notes:

a Descriptive summary statistics based on subject-level raw values, analyzed by the nonparametric Wilcoxon signed-rank test.

b P <0.05 from the parametric two-sided paired t-test for changes from pain state (Visit 2, pretreatment) to pain-free state (Visit 3).

c Descriptive summary statistics based on subject-level raw values, analyzed by the parametric two-sided paired t-test; 95% CIs for the mean change were calculated for these outcomes only.

Abbreviations: CANTAB, Cambridge Neuropsychological Test Automated Battery; mITT, modified intent-to-treat.

Table 3 Mobility assessments during untreated pain state (Visit 2, pretreatment) relative to pain-free state (Visit 3), mITT population

	Paracetamol 500 mg+ caffeine 65 mg (n=6)	Paracetamol 500 mg (n=7)	Placebo (n=7)
Gait, contact phase, s^a
Pain state	n=6	n=7	n=7
Median (range)	0.68 (0.6–0.8)	0.63 (0.6–0.7)	0.73 (0.6–0.8)
Pain-free state	n=6	n=6	n=5
Median (range)	0.64 (0.6–0.8)	0.62 (0.6–0.7)	0.68 (0.6–0.8)
Change (pain vs pain-free)	n=6	n=6	n=5
Median (range)	0.03 (0.0–0.1)	0.02 (0.0–0.1)	0.01 (0.0–0.0)
P-value	0.0313^b	0.2188	0.9999
Gait, stride length, cm^c
Pain state	n=6	n=7	n=7
Mean ± SD	1.49±0.206	1.53±0.189	1.45±0.147
Pain-free state	n=6	n=6	n=5
Mean ± SD	1.55±0.182	1.62±0.254	1.48±0.194
Change (pain vs pain-free)	n=6	n=6	n=5
Mean (95% CI)	−0.06 (−0.17 to 0.04)	−0.08 (−0.21 to 0.05)	−0.02 (−0.07 to 0.02)
P-value	0.1708	0.1568	0.2321
Gait, walking speed, m/s^a
Pain state	n=6	n=7	n=7
Median (range)	1.36 (1.2–1.8)	1.46 (1.3–1.8)	1.34 (1.1–1.6)
Pain-free state	n=6	n=6	n=5
Median (range)	1.48 (1.2–1.9)	1.62 (1.3–2.0)	1.42 (1.1–1.7)
Change (pain vs pain-free)	n=6	n=6	n=5
Median (range)	−0.10 (−0.3 to 0.0)	−0.15 (−0.3 to 0.2)	−0.03 (−0.1 to 0.1)
P-value	0.0625	0.3125	0.4375
Time to stand, s^a
Pain state	n=6	n=7	n=7
Median (range)	1.28 (1.1–1.4)	1.28 (1.0–1.6)	1.37 (1.0–1.7)
Pain-free state	n=6	n=6	n=5
Median (range)	1.18 (1.0–1.7)	1.18 (1.0–1.3)	1.17 (1.0–1.4)
Change (pain vs pain-free)	n=6	n=6	n=5
Median (range)	0.10 (−0.4 to 0.2)	0.13 (−0.2 to 0.3)	0.09 (0.0–0.3)
P-value	0.4375	0.3125	0.1250
Time to stand, ground reaction force, newtons^c
Pain state	n=6	n=7	n=7
Median (range)	624.35 (585.2–822.5)	685.33 (490.0–812.6)	715.19 (553.1–976.4)
Pain-free state	n=6	n=6	n=5
Median (range)	616.04 (591.4–831.9)	669.31 (490.8–919.6)	727.38 (542.5–976.7)
Change (pain vs pain-free)	n=6	n=6	n=5
Median (range)	2.53 (−9.4 to 21.6)	−5.35 (−107.0 to 10.1)	3.21 (−12.2 to 17.3)
P-value	0.5166	0.3184	0.4960
Grip force, kg^c
Pain state	n=6	n=7	n=7
Mean ± SD	27.67±9.145	26.07±8.935	33.90±7.212
Pain-free state	n=6	n=6	n=5
Mean ± SD	29.65±10.043	30.07± 11.179	35.88± 10.098
Change (pain vs pain-free)	n=6	n=6	n=5
Mean (95% CI)	−1.98 (−7.76 to 3.79)	−3.87 (−7.85 to 0.11)	−1.70 (−6.09 to 2.69)
P-value	0.4179	0.0547	0.3426

Notes:

a Descriptive summary statistics based on subject-level raw values, analyzed by the nonparametric Wilcoxon signed-rank test.

b P <0.05 from the two-sided Wilcoxon signed-rank test for changes from pain state (Visit 2, pretreatment) to pain-free state (Visit 3).

c Descriptive summary statistics based on subject-level raw values, analyzed by the parametric two-sided paired t-test; 95% CIs for the mean change were calculated for these outcomes only.

Table 4 Adverse events (AEs)

	Treatment allocation	Timing relative to treatment administration	Severity	Treatment-related
AEs occurring prior to treatment administration
Motorbike accident	Paracetamol	21 days before	Mild	No
Common cold/virus	Placebo	26 days before	Moderate	No
Right knee arthralgia	Placebo	11 days before	Mild	No
Common cold/virus	Placebo	18 days before	Mild	No
AEs occurring after treatment administration
Pharyngeal erythema	Paracetamol	Day of treatment	Mild	No
Worsening hypercholesterolemia	Placebo	10 days after	Mild	No
Acid reflux	Placebo	40 days after	Moderate	No