Pain assessment in hospitalized spinal cord injured patients – a controlled cross-sectional study

2.1 Participants

In-patients at the SCI Centre of Western Denmark were invited to participate. In order to investigate different types of SCI we included 24 SCI patients divided into three subgroups; a) eight sub-acute, traumatic, first time admitted SCI patients (four paraplegics, four tetraplegics), b) eight chronic, traumatic, readmitted SCI patients (two paraplegics, six tetraplegics) and c) eight non-traumatic first time/or re-admitted SCI patients (five paraplegics, three tetraplegics). Early injury was from 0 to 2 year and late injury 2 year and above. This was chosen based on a known high frequency of late development of neuropathic pain, but also a recognized delayed admission of non-traumatic SCI patients to our highly specialized neurorehabilitation hospital.

Inclusion criteria were: age ≥18 years, stable mental health, being able to understand Danish in writing and speech. Furthermore, the patient should report one or several pain problems. Exclusion criteria were: symptoms of severe/moderate dysautonomia, a medical record of significant chronic pain problems prior to SCI, untreated or prior drug abuse or known medical abuse or a diagnosis of hereditary spinal disorder or other types of CNS disease.

The controlgroup were 12 age- and gender-matched able-bodied persons recruited amongst staff at the SCI Centre of Western Denmark and by advertisement on a website. The eligible able-bodied participants had no history of chronic pain problems.

All patients received verbal and written information on the project and their patient rights, and gave informed written and verbal consent to participation. This study has been carried out in accordance with the Declaration of Helsinki, and it has been approved by a local ethical committee (Permission 1-16-02-183-16).

2.2 Methods

The research design was cross-sectional clinical study of SCI in-patients and an able-bodied healthy controlgroup. The examiner interviewed patients and controlpersons, prior to conducting the examination to ensure that participants were enrolled in accordance with the inclusion and exclusion criteria. The questionnaires and examination were scheduled at a later time-point (+24 h) in order to provide time for consideration of any further questions or concerns. Examination of in-patients and healthy controls was done by the same examiner (AR). All participants were examined with three different types of sensory testing using pressure algometry, Von Frey filaments (sensitivity), and repetitive pinprick stimulation (pain windup). The sites of measurements for all examinations were chosen in order to test for a plausible central component in pain regulation. Therefore, the majority of the sites were localized above injury level. All examinations took place with the participant seated in a temperature regulated quiet room.

Additionally, the SCI participants fulfilled the Danish version of McGill Pain Questionnaire (MPQ) [18] and the International SCI Pain Basic Data Set version 2.0 [19], [20] after verbal and written instruction and with the examiner present. The reported pain was then categorized into total pain (Pain Rating Index – Total, PRI-T), affective (PRI-A), sensory (PRI-S), evaluative (PRI-E) or miscellaneous (PRI-M) pain types. In the MPQ, participants also reported present pain intensity (PPI), scored on a six-point scale ranging from “no pain” (0 points) to “excruciating pain” (5 points).

The pressure pain detection threshold (PPDT) and pressure pain tolerance threshold (PPT) were measured using a hand-held pressure algometer (AlgoMed Computerized Pressure Algometer FPIX S/N 10, Medoc Ltd., Ramat Yishai, Israel). Pressure stimuli were applied using a flat, circular probe with a diameter of 1 cm² and with a rate of 30 kPa/s. PPDT was measured in triplets with an interval of at least 15 s between measures at 11 well defined anatomical points, being i) masseter muscle 1.50 cm from angle left/right; ii) temporalis muscle pars media left/right; iii) sternocleidomastoid muscle at mastoid insertion left/right, iv) superior part of trapezius left/right and v) infraspinatus muscle left/right, and vi) left proximal interphalangeal joint (PIP) of the third finger. PPT was performed as a single measurement at two anatomical points: i) masseter muscle 1.50 cm from angle left, and ii) PIP of the third finger left [21], [22].

A set of 20 Von Frey filaments weighted from 0.02 g to 231.50 g were used to examine the detection of cutaneous, mechanical sensitivity. The purpose was to find the Mechanical Detection Threshold (MDT) and the Pain Detection Threshold (PDT). The MDT and PDT were tested in triplets in three anatomically defined areas: i) left cheek (masseter muscle), corresponding to the second trigeminus branch above zygoma, approximately 7 cm from the external ear, halfway between the mouth and lower eyelid, ii) left shoulder, corresponding to m. trapezius superior, iii) Left popliteal fossa (knee pit), in the midline approximately 5 cm below the bend) within a diameter of 2 cm². Pain windup was examined using Von Frey filament number 15 (18.53 g) to perform repetitive pin-prick stimulation within a diameter of 1 cm² at two well-defined anatomical areas; i) dorsum of the left hand and ii) the left cheek. The participant underwent 120 s of stimulation at 0.50 Hz and 2 Hz, with a minimum of 120 s pause between sessions. In order to stimulate with the specific frequencies a Smart Click app was used. During the pin prick test, the subject was asked every 30 s to rate the present pain on a 100 point Visual Analogue Scale [6], [23], [24].

The patient’s medication list was reviewed based on information by the patient and afterwards the examiner and the patient carefully crosschecked the list with the patients’ health records. Based on the WHO Pain Ladder (WHO, 1996 #4102) patients were divided in low (only non-opioids), moderate ([25] non-opioids+weak opioids) and heavily (non-opioids+weak opioids+strong opioids) medicated sub-groups (SCI_low, SCI_mod and SCI_heavy, respectively).

2.3 Statistics

All data were collected and managed using the Research Electronic Data Capture (REDCap©), an electronic data capture tool hosted by Aarhus University, Denmark. Data analyses were performed using STATA15 and Microsoft Excel. Data were imported immediately into REDCap after examinations took place. After data capture was completed, data were exported into STATA and Excel for further analysis. Parametrically distributed data were analyzed using Student´s t-test, and non-parametrical data using Kruskal-Wallis for comparison of several groups or Mann-Whitney U for testing two groups.

For pain windup, regression coefficients of pain as a function of time (seconds) were calculated for SCI patients as well as controls in each of the four sessions (left hand @ 0.50 Hz and 2 Hz, left cheek @ 0.50 Hz and 2 Hz), and compared statistically using tests for linear hypotheses of equality after estimation (Stata15). If a statistically significant difference was present, further analyses were then performed to compare the SCI subgroups’ regression coefficients to the one of the control group.

Primary outcome measures were the difference in PPDT, PPT, MDT and PDT, comparing total SCI group and subgroups to healthy controls. The SCI patients were grouped in various subgroups being; i) sub-acute traumatic, chronic traumatic and non-traumatic, ii) early injury and late injury, and iii) SCI_low, SCI_mod and SCI_heavy. Statistic differences were also investigated between tetraplegics vs. paraplegics and complete vs. incomplete (sensory complete).

Secondary outcome measures were: a) MPQ data, PRI-T, PRI-S, PRI-A, PRI-E, PRI-M, NWC, PPI in SCI subgroups [18] and b) pain distribution and clinical pain response in medication subgroups [26], [27].

Unless specified otherwise, data are presented as means±SD.

3.1 Pain

All 24 SCI patients presented with at least one significant pain problem, and 21 (87.50%) patients presented neuropathic pain problems. Analyses of the Danish version of MPQ showed significantly higher PPI in chronic and non-traumatic SCI patients compared to sub-acute traumatic SCI patients (3.13±0.99, 1.75±1.75 and 0.13±0.35, respectively, p≤0.0047. Fig. 1), but no significant differences were observed regarding pain subcategories between the SCI groups. Neither was difference regarding McGill Pain scores seen when comparing complete and incomplete groups and comparing paraplegics vs. tetraplegics. However incomplete SCI patients had significantly higher on-going pain (t-test; p<0.05)

Fig. 1:

Reported present pain intensity in three subgroups of spinal cord injury patients. *Significant difference (p<0.05).

3.2 Pressure pain

PPDT was significantly reduced above level of lesion in SCI patients as compared with healthy controls (Masseter, left: 189.40±90.60 vs. 283.50±102.50 kPa/cm²; Infraspinatus, left: 612.0±382.40 vs. 733.00±293.50 kPa/cm², respectively. p<0.05 Fig. 2). Additionally, PPT at PIP of the third finger was lower in SCI patients. No significant differences were found between SCI patients and controls in the remaining measure points.

Fig. 2:

The pressure pain detection threshold of spinal cord injury patients and able-bodied controls at several anatomical areas, measured by pressure algometry. *Significant difference from controls (p<0.05). **Significant difference from controls (p<0.01).

A significant difference in bilateral PPDT for sternocleidomastoid, trapezius and infraspinatus and total PPDT was found when comparing SCI_low with SCI_heavy (see Table 2). PPT was also significantly lower for SCI_low, compared to SCI_heavy.

Table 2:

Pressure algometry and medication in SCI in-patients subgroups and controls.

1. The bilateral pressure pain detection (PPDT) and tolerance thresholds (PPT) of spinal cord injury patients and able-bodied controls at distinct anatomical areas, grouped by level of medication usage. The control group data are presented for reference; they have not been included in the analyses. PIP=proximal interphalangeal joint of the third finger on left hand; SCIlow=low-medicated SCI group; SCImed=moderately-medicated SCI group; SCIheavy=heavily-medicated SCI group. ^aSignificant difference (p<0.05). ^bSignificant difference (p<0.01). Bold values denote total PPDT: sum score of 5 paired muscles.

Additionally, the value of PPT, PIP and PPT masseter were found to be significantly lower in non-traumatic SCI compared to the control group similar to early injury SCI compared to control group. No further significance was found in PPDT or PPT of the remaining measure points when comparing the remaining SCI subgroups with control group. No further difference was found between complete and incomplete groups or tetraplegics in comparison to paraplegics.

3.3 Mechanical sensitivity

The SCI patients showed a significantly higher MDT below injury compared to controls [left popliteal; 3.43 (0.23, 38.75) g vs. 0.19 (0.02, 0.62) g respectively, medians (10th, 90th percentiles), Mann-Whitney U: p=0.0005] as well as above the injury [left cheek, 0.05 (0.02, 0.23) vs. 0.02 (0.02, 0.05), p=0.004]. No significant differences were found amongst the PDT measurements.

In comparison with control group all three SCI groups displayed significantly higher MDT on the left cheek, yet no significant differences were found between the subgroups. Due to a large number of missing measurements of PDT, no proper values were available for analyses between subgroups. No MDT differences or PDT differences were obtained between para and tetraplegics and between complete and incomplete SCI patients.

3.4 Pain windup

Pain windup during repetitive pinprick was found in the SCI group as well as in the control group. A significant increase in reported pain (VAS) from 0 s to 120 s was found on the left hand at 0.50 Hz and 2 Hz, and on the left cheek at 0.50 Hz and 2 Hz in both groups. When comparing regression coefficients of the pain windup in the SCI group to that of the control group, minor yet significant differences were found at the left hand at 0.50 Hz (0.0063 vs. 0.0061 cm VAS/s for SCI and controls, respectively. p<0.05) and 2 Hz 0.01072 vs. 0.01139. p<0.01) stimulation, as well as at the left cheek at 2 Hz (0.01125 vs. 0.01444, p<0.01).

A significantly higher reported VAS pain at 120 s was found in i) the non-traumatic SCI subgroup compared to controls, ii) chronic SCI subgroup compared to controls and iii) SCI_low compared to SCI_heavy. However, when comparing pain windup coefficients, the sub-acute and non-traumatic subgroups displayed a lesser pain windup than controls, and the chronic SCI subgroup mainly displayed a higher pain windup (Fig. 3); this indicates that the higher VAS pain reported at 120 s is mainly due to a higher current level of reported pain.

Fig. 3:

The reported pain at 0, 30, 60, 90 and 120 s during repetitive pinprick stimulation. Dotted lines represent linear trend estimations. *Significantly lower coefficient than controls (p<0.05). †Significantly higher coefficient than controls (p<0.05).