Somatosensory sensitivity and postoperative endogenous pain modulation have not been investigated in temporomandibular joint (TMJ) prosthesis patients. The objectives of this study were to assess somatosensory function at the TMJ and examine possible differences in conditioned pain modulation (CPM) between patients with total TMJ prostheses ( n = 7) and a reference group of healthy controls ( n = 20). Somatosensory abnormalities were assessed using quantitative sensory testing (QST), which encompasses thermal and mechanical testing procedures. CPM was tested by comparing pressure pain thresholds (PPT) before (baseline), during, and after the application of painful and non-painful cold stimuli. PPTs were measured at the TMJ and thenar eminence (control). The effect of CPM on PPT values was tested with analysis of variance. Three patients exhibited mixed somatosensory loss (i.e., decreased thermal and mechanical detection) with mixed hyperalgesia (i.e., increased sensitivity to thermal and mechanical pain) and two patients exhibited mixed loss with only mechanical hyperalgesia. There was a significant decrease in pressure pain sensitivity at both sites during painful cold application in healthy controls ( P < 0.001) but not in patients ( P = 0.476). In conclusion, QST measures demonstrated somatosensory abnormalities in patients with total TMJ prostheses. Noxious conditioning cold stimuli evoked CPM-like effects in healthy subjects but not in patients with TMJ reconstruction.
The temporomandibular joint (TMJ) is among the most complicated articulations in the body. Total alloplastic TMJ replacement is a biomechanical solution for the treatment of end-stage disease. However, replacement of the TMJ apparatus is only considered when all other treatment modalities including conservative, non-surgical, and surgical therapies have been used. Indications for total TMJ reconstruction are ankylosed or resorbed joints with severe anatomical abnormalities, severe inflammatory arthritic disease, previously failed alloplastic reconstruction, and failed autogenous grafts in multiply operated patients. Irrespective of the specific indication, the main aim of TMJ reconstruction is to restore the form and function of the joint, with the relief of pain as a secondary benefit.
Although studies on TMJ reconstruction have indicated improvements in subjective and objective parameters after replacement, many postoperative complications have been identified. These complications include pain, infection, heterotopic bone deposition, nerve damage, haematoma formation, salivary fistula, and malocclusion. Many studies have reported a reduction in pain after joint reconstruction, but unfortunately, complete elimination of pain has not been mentioned in the literature. Therefore, considering that pain is one of the most common complications, this study was performed to provide a better understanding of the pain mechanism involved in these patients.
The assessment of positive and negative somatosensory signs and symptoms in relation to pain complaints is one of the first steps towards a better understanding of pain mechanisms. The standardized quantitative sensory testing (QST) battery introduced by the German Research Network on Neuropathic Pain (DFNS), consisting of 13 parameters, can assess somatosensory function through sensory loss (small and large nerve fibre function) and sensory gain (hyperalgesia, allodynia, and hyperesthesia). The QST battery tests different sub-modalities of nerve fibres involved in the transduction of sensory information from the periphery to the spinal cord, such as Aβ-fibres, Aδ-fibres, and C-fibres. It can also be used to quantitate changes in somatosensory neural function. In addition, defective endogenous pain inhibitory systems are proposed to play an important role in the development of persistent pain.
Conditioned pain modulation (CPM) paradigms can assess the function of endogenous pain inhibitory pathways in humans. CPM can also be used to predict ongoing pain, as well as the risk of future chronic pain, including chronic postoperative pain. CPM testing generally involves the use of two simultaneous stimuli (conditioning and test stimulus) to estimate the resultant pain inhibition of the test stimulus. To date, no studies have assessed postoperative somatosensory sensitivity and pain modulatory effects in TMJ prosthesis patients.
The aims of the present study were (1) to assess the somatosensory function at and around the TMJ in patients with total TMJ prostheses, and (2) to examine the possible differences in conditioned pain modulation between the patients with total TMJ prostheses and healthy controls.
Materials and methods
This case-series study included seven consecutive patients (five women, two men) who had undergone a total joint reconstruction with a Biomet Total TMJ Replacement System at the study institution. Patients who had undergone a TMJ reconstruction at another hospital were excluded.
Out of seven patients, five had bilateral prostheses and two had a unilateral prosthesis. Indications for TMJ reconstruction were ankylosis in six patients and resection of the mandibular ramus because of a keratocystic odontogenic tumour in one patient. The average age of the patients at the time of surgery was 46 years (range 26–59 years). The prostheses were placed in an average 6 years (range 4–9 years) before the follow-up examination. Twenty healthy controls (11 women, nine men) with no signs of a temporomandibular disorder (TMD) or musculoskeletal or rheumatologic disease were recruited; their average age was 32 years (range 21–47 years). All patients and healthy controls gave their written informed consent prior to study participation, in accordance with the Declaration of Helsinki. The study was approved by the local ethics committee in Denmark.
The TMJ implant used in this study was the Biomet Total TMJ Replacement System. This implant system is a two-component stock system consisting of mandibular condyle and glenoid fossa components. The components were attached to the bone with titanium screws.
The surgical procedure used involved a submandibular incision and a pre-auricular incision. An osteotomy was performed at the neck of condyle and then the condyle was removed. Another osteotomy was performed at the articular eminence and a perfect fit of the fossa prosthesis dummy was obtained. The fossa prosthesis was fixed with screws. Intermaxillary fixation using arch bars was then performed. For the resection of the lateral part of the ramus, the dummy of the condylar prosthesis served as a guide. The mandibular prosthesis was then fixed with screws with the condylar head in the fossa prosthesis on the remaining ramus. The intermaxillary fixation was removed and the extraoral approaches were sutured. The patients were readmitted for follow-up controls after 1 week, 1 month, 3 months, and 12 months.
In the present study, the subjective assessment of pain, neurosensory assessment using QST, and endogenous pain modulation (CPM) were assessed in all of the patients and healthy controls during a follow-up examination, at an average 6 years after placement of the prostheses. The neurosensory assessment and surgical procedures were not performed by the same surgeon.
Subjective assessment of pain
Characteristic pain intensity (CPI) is a self-report measure derived from the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) history questionnaire. It appraises current pain, average pain, and worst pain in the jaw during the last 6 months. The resulting CPI score ranges from 0 to 100, with 100 being the most pain.
Quantitative sensory testing (QST)
A standardized battery of QST was performed according to the protocol of the DFNS. The QST battery consists of seven tests measuring 13 parameters that cover relevant nerve function. For a detailed description of the protocol, see Rolke et al. In summary, the protocol investigates the following sensory functions: (1) thermal thresholds: cold detection (CDT), warm detection (WDT), cold pain (CPT), heat pain (HPT), and thermal sensory limen (TSL); (2) mechanical thresholds: mechanical detection (MDT), vibration detection (VDT), mechanical pain (MPT), and pressure pain (PPT); (3) stimulus–response functions: mechanical pain sensitivity (MPS), dynamic mechanical allodynia (DMA), wind-up ratio (pain summation to repetitive pinprick) (WUR), and paradoxical heat sensations (PHS) during the thermal limen procedure.
QST was performed on the skin overlying the TMJ on both sides in all patients and healthy controls. In patients, the most painful side was defined as the test site and the non-painful or less painful side was defined as the control site.
Thermal detection and pain thresholds and the number of paradoxical heat sensations
As a measure of Aδ-fibre function, thresholds for cold detection (CDT) and cold pain (CPT) were assessed. C-fibre function was tested by assessing thresholds for warmth detection (WDT). Heat pain thresholds (HPT) determined with contact thermal stimulators are considered to assess mainly Aδ-fibre function in skin. The presence of paradoxical heat sensations upon cold stimulation is usually considered indicative of a disturbance in Aδ-cold fibre function or of central sensitization.
All thermal testing was performed using a PATHWAY thermal sensory testing device (Medoc Ltd., Ramat Yishai, Israel). The baseline temperature was 32 °C and the contact area of the thermode was 30 mm × 30 mm (square surface). The cut-off temperature for cold stimuli (CDT, CPT) was 0 °C, and for warm and hot stimuli (WDT, HPT) was 50 °C. CDT, WDT, paradoxical heat sensations by thermal sensory limen procedure (TSL), CPT, and HPT were assessed using ramped stimuli of 1 °C/s. For all thresholds, the mean of three threshold temperature measurements was calculated.
Mechanical detection threshold
To assess Aβ-fibre function, mechanical detection thresholds (MDT) were measured using a set of standardized von Frey filaments with rounded tips of 0.5-mm diameter (OptiHair 2 ; MARSTOCKnervtest, Marburg, Germany). The OptiHair 2 set contains 12 monofilaments, which exerts forces between 0.25 and 512 mN. The monofilament was applied perpendicularly to the examination site; the contact time was 1–2 s. Using the ‘method of limits’, five threshold determinations were made, each with a series of ascending and descending stimulus intensities. The final threshold was the geometric mean of these five series.
Mechanical pain threshold
To assess Aδ-fibre function in relation to mechanical stimuli, weighted pinprick stimulators (cylindrical tip, 0.25-mm diameter) with fixed stimulus intensities (8, 16, 32, 64, 128, 256, and 512 mN) were used to determine the mechanical pain threshold (MPT). All pinprick tests were done with the stimulator perpendicular to the examination site. The method of limits that was used to determine the MDT was also used to determine MPT.
Stimulus–response function: mechanical pain sensitivity for pinprick stimuli and dynamic mechanical allodynia
Here sensitivity to sharp stimuli (as mediated by Aδ-fibres) and pain upon light stroking were measured. Two sets of instruments were used for this stimulus–response assessment. To determine mechanical pain sensitivity (MPS), seven weighted pinprick stimulators were used. The pinprick stimulators and the application technique were the same as those used to determine MPT. Three tactile stimulators were used to determine DMA : (1) a cotton wisp that exerted a force of ∼3 mN, (2) a cotton wool tip (Q-tip) attached to a flexible handle that exerted a force of ∼100 mN, and (3) a disposable toothbrush (Top Dent; Meda AB, Solna, Sweden) that exerted a force of ∼200 mN. The tactile stimulator was applied in a single stroke over about 1–2 cm in length of skin. A series of 10 measurements was made five times, each with the 10 stimulators (seven pinprick and three tactile stimulators) applied in a different order, as specified in the DFNS protocol. For each of the resulting 50 stimuli, the subject chose a pain rating on a 0–100-point numerical rating scale (NRS) with the endpoints ‘0′ indicating ‘no pain’ and ‘100′ indicating ‘most intense pain imaginable’. MPS was calculated as the geometric mean of all numerical ratings for pinprick stimuli. DMA was calculated as the geometric mean of all numerical ratings for tactile stimuli.
Wind-up ratio to repetitive pinprick stimuli
To measure the perceptual correlate of temporal pain summation, the wind-up ratio (WUR) for repetitive pinprick stimuli was assessed. The perceived magnitude of a single pinprick stimulus was compared to that of a train of 10 pinprick stimuli with the same force, repeated at a rate of 1/s and kept constant using a metronome (MA-30 digital metronome; KORG, Tokyo, Japan). The custom-made set of seven pinprick stimulators (delivering forces of 8, 16, 32, 64, 128, 256, and 512 mN) used in the MPT determinations were used for WUR assessment.
The instrument that delivered a force that the subject perceived as ‘slightly painful’ was chosen for the tests and could vary from site to site and from individual to individual. To determine which instrument the subject perceived to be slightly painful, the 128-mN stimulator was tried first. If the response was 0 (not painful), the test was repeated with the next stimulator in the series that exerted a stronger force. If the subject perceived the stimulus as intolerable, the next stimulator in the series that exerted a weaker force was used. Otherwise, if the subject’s numerical response was >0, indicating pain, but not intolerable pain, the stimulator was selected for testing at that site. If a subject did not perceive the 512-mN stimulator to be painful, the test was abandoned. Five single pinprick stimuli were alternated with five trains of 10 stimuli. The mean pain rating of the trains was then divided by the mean pain rating for single stimuli to render a WUR that represented temporal pain summation for the site.
Vibration detection threshold
One way of assessing Aβ-fibre function is to determine the vibration detection threshold (VDT) using a Rydel–Seiffer graded tuning fork (64 Hz, 8/8 scale). VDT represents the only disappearance threshold within the proposed QST battery. The tuning fork was placed over a bony prominence and the subject indicated when the vibration could no longer be sensed. On the 9-point (0–8 out of 8) scale measuring intensity of vibration, values with a discrimination down to 0.5 were noted. The mean of three trials was calculated.
Pressure pain threshold
The pressure pain threshold (PPT) is the final test in the protocol. It was measured to test deep pain sensitivity, which is probably mediated through C- or Aδ-fibres. A digital pressure algometer (SOMEDIC AB, Sollentuna, Sweden) with a probe area of 1 cm 2 was used. During the test, pressure was increased at a rate of 50 kPa/s. At the first painful sensation, the subjects pressed a button to interrupt stimulation and the PPT was defined as the amount of pressure (kPa) at which the subject first perceived pain. The PPT was determined as the mean of three recordings.
Conditioned pain modulation (CPM)
CPM is a non-invasive test of the endogenous pain-inhibitory system using a heterotopic noxious conditioning stimulation paradigm. The pressure pain threshold (PPT) was assessed in triplicate using a pressure algometer before (baseline), during, and after the application of a noxious conditioning cold stimulus (cold pressor test: immersion of the subject’s foot in ice water maintained at 2–5 °C) and non-noxious conditioning stimulus (neutral water maintained at 26–28 °C). At first, PPT ratings were obtained at baseline on the dominant side of the TMJ and thenar muscle (control). In patients, the dominant side was defined as the most painful TMJ side. Immediately following this baseline assessment, subjects underwent the cold pressor test. During this test, subjects immersed their dominant leg up to the ankle in a cold water bath maintained at 2–5 °C for 3 min. After 1.5 min of leg immersion, PPT was re-assessed at the TMJ and thenar muscle (i.e., the same site as the baseline assessment). During leg immersion, subjects were also asked to rate the pain intensity and the unpleasantness using a NRS of 0–100, where ‘0′ indicated ‘no pain’ and ‘100′ indicated ‘most intense pain imaginable’. After 3 min the subjects removed their leg from the water. Soon after the cold pain disappeared, the PPT was again measured at the TMJ and thenar muscle.
After an interval of 12–15 min, the same procedure was repeated using neutral water/non-painful water as conditioning stimulus. Here again, PPT readings were obtained in triplicate before, during, and after the application of the conditioning stimulus. Subjects also rated the pain intensity and unpleasantness on the 0–100 NRS during the leg immersion in neutral water. The sequence of immersion of leg in ice or neutral water was randomized ( Fig. 1 ).