Nadine Khawaja

Case studies on implant removal influencing the resolution of inferior alveolar nerve injury

Introduction Nerve injury during implant placement is a preventable, serious complication with major medico-legal implications. The incidence of implant related inferior alveolar nerve (IAN) injuries varies from 0-40%. This article presents four cases of IAN injury following mandibular implant placement with early removal, referred to the oral surgery department, Kings College Hospital, London.Objectives To assess sensory disturbance and recovery in patients with implant related IAN injury and assess whether early removal of the implants promotes neural recovery. To present recommendations on how to best deal with suspected/actual nerve injuries and prevent their occurrence.Methods Over the last two years, four patients referred for specialist opinion to the oral surgery department were identified as having sustained implant related IAN injury with early removal (18 hours to four days post-injury). Data were collected by referral to health records.Results All patients suffered from numbness of the affected inferior alveolar dermatome with three out of four cases also experiencing some form of neuropathic pain. Cases 1 and 2, who had their implants removed at 18 and 36 hours post-injury respectively, regained almost complete sensory recovery. Case 1 also had adjunctive NSAID and steroid therapy. Cases 3 and 4 suffered complete numbness in the inferior alveolar dermatome and did not experience any improvement in sensation following removal of their implants at two and four days post-injury respectively. Both patients with significant persistent neuropathy (Cases 3 &4) reported functional problems.Conclusion This cohort of patients may demonstrate that early removal of implants associated with IAN injury (less than 36 hours post-injury) may assist in minimising or even resolution of IAN neuropathy. Adjunctive corticosteroid and high dose non-steroidal anti-inflammatory therapy also appears effective. Implant related IAN injury is a preventable, elective procedure and a suggested protocol of management of suspected injuries, for dental practitioners, is presented.

Beyond Patient Reported Pain: Perfusion Magnetic Resonance Imaging Demonstrates Reproducible Cerebral Representation of Ongoing Post-Surgical Pain

Development of treatments for acute and chronic pain conditions remains a challenge, with an unmet need for improved sensitivity and reproducibility in measuring pain in patients. Here we used pulsed-continuous arterial spin-labelling [pCASL], a relatively novel perfusion magnetic-resonance imaging technique, in conjunction with a commonly-used post-surgical model, to measure changes in regional cerebral blood flow [rCBF] associated with the experience of being in ongoing pain. We demonstrate repeatable, reproducible assessment of ongoing pain that is independent of patient self-report. In a cross-over trial design, 16 participants requiring bilateral removal of lower-jaw third molars underwent pain-free pre-surgical pCASL scans. Following extraction of either left or right tooth, repeat scans were acquired during post-operative ongoing pain. When pain-free following surgical recovery, the pre/post-surgical scanning procedure was repeated for the remaining tooth. Voxelwise statistical comparison of pre and post-surgical scans was performed to reveal rCBF changes representing ongoing pain. In addition, rCBF values in predefined pain and control brain regions were obtained. rCBF increases (5–10%) representing post-surgical ongoing pain were identified bilaterally in a network including primary and secondary somatosensory, insula and cingulate cortices, thalamus, amygdala, hippocampus, midbrain and brainstem (including trigeminal ganglion and principal-sensory nucleus), but not in a control region in visual cortex. rCBF changes were reproducible, with no rCBF differences identified across scans within-session or between post-surgical pain sessions. This is the first report of the cerebral representation of ongoing post-surgical pain without the need for exogenous tracers. Regions of rCBF increases are plausibly associated with pain and the technique is reproducible, providing an attractive proposition for testing interventions for on-going pain that do not rely solely on patient self-report. Our findings have the potential to improve our understanding of the cerebral representation of persistent painful conditions, leading to improved identification of specific patient sub-types and implementation of mechanism-based treatments.

Cerebral analgesic response to nonsteroidal anti-inflammatory drug ibuprofen.

Abstract Nonopioid agents, such as nonsteroidal anti-inflammatory drugs (NSAIDs), are the most commonly used class of analgesics. Increasing evidence suggests that cyclooxygenase (COX) inhibition at both peripheral and central sites can contribute to the antihyperalgesic effects of NSAIDs, with the predominant clinical effect being mediated centrally. In this study, we examined the cerebral response to ibuprofen in presurgical and postsurgical states and looked at the analgesic interaction between surgical state and treatment. We used an established clinical pain model involving third molar extraction, and quantitative arterial spin labelling (ASL) imaging to measure changes in tonic/ongoing neural activity. Concurrent to the ASL scans, we presented visual analogue scales inside the scanner to evaluate the subjective experience of pain. This novel methodology was incorporated into a randomized double-blind placebo-controlled design, with an open method of drug administration. We found that independent of its antinociceptive action, ibuprofen has no effect on regional cerebral blood flow under pain-free conditions (presurgery). However, in the postsurgical state, we observed increased activation of top–down modulatory circuits, which was accompanied by decreases in the areas engaged because of ongoing pain. Our findings demonstrate that ibuprofen has a measurable analgesic response in the human brain, with the subjective effects of pain relief reflected in two distinct brain networks. The observed activation of descending modulatory circuits warrants further investigation, as this may provide new insights into the inhibitory mechanisms of analgesia that might be exploited to improve safety and efficacy in pain management.

Quantifying the test–retest reliability of cerebral blood flow measurements in a clinical model of on-going post-surgical pain: A study using pseudo-continuous arterial spin labelling

Arterial spin labelling (ASL) is increasingly being applied to study the cerebral response to pain in both experimental human models and patients with persistent pain. Despite its advantages, scanning time and reliability remain important issues in the clinical applicability of ASL. Here we present the test–retest analysis of concurrent pseudo-continuous ASL (pCASL) and visual analogue scale (VAS), in a clinical model of on-going pain following third molar extraction (TME). Using ICC performance measures, we were able to quantify the reliability of the post-surgical pain state and ΔCBF (change in CBF), both at the group and individual case level. Within-subject, the inter- and intra-session reliability of the post-surgical pain state was ranked good-to-excellent (ICC > 0.6) across both pCASL and VAS modalities. The parameter ΔCBF (change in CBF between pre- and post-surgical states) performed reliably (ICC > 0.4), provided that a single baseline condition (or the mean of more than one baseline) was used for subtraction. Between-subjects, the pCASL measurements in the post-surgical pain state and ΔCBF were both characterised as reliable (ICC > 0.4). However, the subjective VAS pain ratings demonstrated a significant contribution of pain state variability, which suggests diminished utility for interindividual comparisons. These analyses indicate that the pCASL imaging technique has considerable potential for the comparison of within- and between-subjects differences associated with pain-induced state changes and baseline differences in regional CBF. They also suggest that differences in baseline perfusion and functional lateralisation characteristics may play an important role in the overall reliability of the estimated changes in CBF. Repeated measures designs have the important advantage that they provide good reliability for comparing condition effects because all sources of variability between subjects are excluded from the experimental error. The ability to elicit reliable neural correlates of on-going pain using quantitative perfusion imaging may help support the conclusions derived from subjective self-report.

Case studies illustrating the management of trigeminal neuropathic pain using topical 5% lidocaine plasters

Chronic trigeminal pain, with its severe related functional problems, is difficult to treat. Treatment is often empirically based on medications used for other chronic pain conditions. Systemic sodium channel and calcium channel blocking agents may cause a multitude of complications that are often poorly tolerated by the patient. Aim: The aim of this case report was to assess the efficacy of topical 5% lidocaine plasters in reducing pain and reducing adjuvant medication in patients with orofacial neuropathic pain. Method: Fourteen patients with chronic orofacial pain conditions referred to the oral surgery department were instructed to wear 5% lidocaine plasters for 12 hours each day over the painful area. The conditions included post-surgical neuropathy (n = 10), multiple sclerosis-related pain (n = 1), persistent idiopathic facial pain (n = 1), Ramsay Hunt syndrome (post-herpetic neuralgia, n = 1) and trigeminal neuralgia (n = 1). Data were collected on patient demographics, pain levels and medication. Results: Pain levels improved in 12 out of 14 patients. Nine patients had a reduction in adjuvant medication, two of whom completely stopped adjuvant treatment. Conclusion: This case series demonstrates that of the use of 5% lidocaine plasters may play a useful role in the management of chronic trigeminal pain. A suggested novel approach for the management of orofacial pain, for clinicians, is presented. Summary points Management of chronic orofacial pain continues to be a major challenge to the clinician. Patients are often placed on a multitude of medications in an attempt to alleviate pain without success. Topical 5% lidocaine plasters, currently used for the management of post-herpetic neuralgia, offer the option of locally targeting trigeminal pain without the multiple side-effects of systemic medication. This case series demonstrates that lidocaine plasters decrease verbal pain scores in extraoral, trigeminal and neuropathic pain, and reduce the use of other neuromodulatory agents in some, but not all, patients. The plasters should be considered as a useful adjuvant in the management of pain in these patients.

Multivariate decoding of cerebral blood flow measures in a clinical model of on-going postsurgical pain

Recent reports of multivariate machine learning (ML) techniques have highlighted their potential use to detect prognostic and diagnostic markers of pain. However, applications to date have focussed on acute experimental nociceptive stimuli rather than clinically relevant pain states. These reports have coincided with others describing the application of arterial spin labeling (ASL) to detect changes in regional cerebral blood flow (rCBF) in patients with on‐going clinical pain. We combined these acquisition and analysis methodologies in a well‐characterized postsurgical pain model. The principal aims were (1) to assess the classification accuracy of rCBF indices acquired prior to and following surgical intervention and (2) to optimise the amount of data required to maintain accurate classification. Twenty male volunteers, requiring bilateral, lower jaw third molar extraction (TME), underwent ASL examination prior to and following individual left and right TME, representing presurgical and postsurgical states, respectively. Six ASL time points were acquired at each exam. Each ASL image was preceded by visual analogue scale assessments of alertness and subjective pain experiences. Using all data from all sessions, an independent Gaussian Process binary classifier successfully discriminated postsurgical from presurgical states with 94.73% accuracy; over 80% accuracy could be achieved using half of the data (equivalent to 15 min scan time). This work demonstrates the concept and feasibility of time‐efficient, probabilistic prediction of clinically relevant pain at the individual level. We discuss the potential of ML techniques to impact on the search for novel approaches to diagnosis, management, and treatment to complement conventional patient self‐reporting. Hum Brain Mapp 36:633–642, 2015.

118 MAGNETIC RESONANCE PERFUSION IMAGING DEMONSTRATES CEREBRAL REPRESENTATION OF ONGOING PAIN FOLLOWING THIRD MOLAR EXTRACTION

• Preprocessing and voxelwise image analysis performed using FSL (http://www.fmrib.ox.ac.uk/fsl ) • Mean rCBF values derived for each subject in each session extracted from probabilistic ROI masks using fslview Magnetic Resonance Perfusion Imaging Demonstrates Cerebral Representation of Ongoing Pain Following Third Molar Extraction Kristina Krause 1,2, Matthew Howard 2, Nadine Khawaja3, Natalie Massat4, John Huggins, 4 Gunter Schumann 1, Steve Williams2, Tara Renton3