Experiences of diagnosis and treatment for upper limb Complex Regional Pain Syndrome: a qualitative analysis.

INTRODUCTION: Complex Regional Pain Syndrome (CRPS) most frequently affects the upper limb, with high associated disability. Delays to diagnosis and appropriate treatment can adversely impact prognosis and quality of life, but little is known about the healthcare experiences of people with CRPS. This study aimed to explore lived experiences of diagnosis and treatment for people with upper limb CRPS. METHODS: Participants were recruited through online support groups and multiple public and private healthcare settings in the Greater Wellington Region, New Zealand. Semi-structured interviews were conducted with participants who had experienced upper limb CRPS for more than three months and less than three years. Interviews were transcribed verbatim and analysed using reflexive thematic analysis. RESULTS: Thirteen participants (11 female, 2 male) aged between 43 and 68 years were interviewed. Duration of CRPS ranged from 7 months to 2.5 years. Five themes were identified. Participants initially engaged in healthcare out of a desire to return to being the person they were before having CRPS. Three interacting experiences epitomised the overall healthcare experience: (1) not knowing what is going on, (2) not being taken seriously, and (3) healthcare as adding another layer of load. Meanwhile, participants used multiple approaches in an attempt to not let CRPS stop them from continuing to live their lives. CONCLUSIONS: Participants in this study felt that credible information, validation, and simplification from healthcare providers and systems would support their process of navigating towards a meaningful life and self-concept in the presence of CRPS.

Baseline predictors related to functional outcomes in patients older than sixty years with complex regional pain syndrome type 1 after distal radius fracture treated conservatively: a prospective observational study.

PURPOSE: This study aimed to analyze baseline predictors of functional outcomes six weeks and at one year follow-up in patients older than 60 years with complex regional pain syndrome type 1 (CRPS I) after distal radius fracture (DRF). METHODS: A total of 120 patients with CRPS I after DRF were prospectively recruited. Presumptive relevant factors were collected and analyzed as potential baseline predictors. Additionally, functional outcomes were assessed at the beginning of physiotherapy treatment, at six weeks after finishing physiotherapy treatment, and at one year follow-up. Patient-Rated Wrist Evaluation; Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire; Jamar dynamometer; and visual analog scale (VAS) were assessed. RESULTS: All participants completed the study. At 6 weeks, the main results showed an association of lower values of grip strength with female sex (p = 0.010), intra-articular DRFs (p = 0.030), longer immobilization time (p = 0.040), lower levels of physical activity (p < 0.001), higher levels of kinesiophobia (p = 0.010), and anxiety (p = 0.020). At 1-year follow-up, the results showed an association of lower values of DASH with higher BMI (p < 0.001) and longer immobilization time (p < 0.001); and higher values of VAS showed an association with older age (p = 0.010), higher BMI (p = 0.010), and lower levels of physical activity (p = 0.040). CONCLUSION: At six weeks, factors such as BMI, immobilization time, physical activity, and kinesiophobia are associated with lower functional outcomes. Additionally, at one year follow-up, BMI, immobilization time, and physical activity continue to be associated with lower functional outcomes in patients with CRPS I after DRF treated conservatively.

Incidence and risk factors for complex regional pain syndrome in radius fractures: meta-analysis.

PURPOSE: This meta-analysis aimed to evaluate the incidence and risk factors for complex regional pain syndrome (CRPS) in radius fractures. METHODS: The meta-analysis was performed using the PubMed, Embase, Scopus, and Cochrane Collaboration Library databases. Studies focusing on patients with conservative or surgically treated radius fractures leading to CRPS were included. A control group consisting of patients with radius fractures and no CRPS (-) was included. The outcome measures were incidence and risk factors. Comparative studies were also included. Data were combined using Review Manager 5.4. RESULTS: Out of 610 studies, nine studies were included. The incidence of CRPS after radius fractures ranged from 0.19 to 13.63% (95% CI: 11.12-16.15%). Open fractures, high-energy mechanisms in radial head fractures, and associations with ulnar fractures were risk factors for CRPS [(RR: 0.98; 95% CI: 0.97-1.00), (RR: 0.18; 95% CI: 0.07-0.47), and (RR: 1.25; 95% CI: 1.17-1.35), respectively]. Other risk factors were female sex and high body mass index [(RR: 1.20; 95% CI: 1.05-1.37) and (MD: 1.17; 95% CI: 0.45-1.88)]. Psychiatric factors also increased the incidence of CRPS (RR: 2.04; 95% CI: 1.83-2.28). On the other hand, the type of surgery (external fixation or open reduction and internal fixation) and manipulations; associated comorbidities (diabetes and hypertension) together with tobacco and alcohol abuse; marital status, educational level, employment status, and socioeconomic status were not risk factors (p > 0.05). CONCLUSION: The incidence of CRPS in radius fractures was 13.63%. Fractures with greater complexity or greater associated tissue damage, female sex, high BMI, and psychiatric disorders were risk factors for the development of CRPS. LEVEL OF EVIDENCE: Meta-analysis of cohort and case series studies; II.

Olfaction in Complex Regional Pain Syndrome.

OBJECTIVE: Complex regional pain syndrome (CRPS) is associated with a range of sensory disturbances on the symptomatic side of the body but whether this includes olfaction is uncertain. To clarify this, the aims of this study were to compare ratings of intensity and hedonic appeal of household odorants in CRPS patients and controls, and to determine whether ratings differed between the symptomatic and contralateral sides within the sample of patients. METHODS: Six odorants (vanilla, fish sauce, vinegar, eucalyptus, almond essence and acetone) were presented sequentially in random order on cottonwool buds held in the midline approximately 1 cm from both nostrils in 37 CRPS patients and 21 pain-free controls. Each odor was rated for intensity and hedonic appeal, and participants reported whether the odor was stronger and/or smelt different on one side than the other. RESULTS: The odorants smelt worse for patients than controls (P < .05 for the symptomatic and contralateral sides) but neither the intensity nor the unpleasantness of the odorants was greater on the symptomatic than contralateral side in the group as-a-whole. CONCLUSIONS: These findings suggest that the trigeminal component of olfaction interacts bilaterally with pain-sensitized circuits in the thalamus or higher cortical centers to distort odor perception in patients with CRPS. This aberrant process appears to differ from the mechanism that underlies hemilateral hyperalgesia in other sensory modalities.

Auditory disturbances in patients with complex regional pain syndrome.

ABSTRACT: Complex regional pain syndrome (CRPS) is often associated with reduced sound tolerance (hyperacusis) on the affected side, but the mechanism of this symptom is unclear. As compensatory increases in central auditory activity after cochlear injury may trigger hyperacusis, hearing and discomfort thresholds to pure tones (250, 500, 1000, 2000, 3000, 4000, 6000, and 8000 Hz) were assessed in 34 patients with CRPS and 26 pain-free controls. In addition, in 31 patients and 17 controls, auditory-evoked potentials to click stimuli (0.08 ms duration, 6 Hz, 60 dB above the hearing threshold) were averaged across 2000 trials for each ear. Auditory discomfort thresholds were lower at several pitches on the CRPS-affected than contralateral side and lower at all pitches on the affected side than in controls. However, ipsilateral hyperacusis was not associated with psychophysical or physiological signs of cochlear damage. Instead, neural activity in the ipsilateral brainstem and midbrain was greater when repetitive click stimuli were presented on the affected than contralateral side and greater bilaterally than in controls. In addition, click-evoked potentials, reflecting thalamo-cortical signal transfer and early cortical processing, were greater contralaterally in patients than controls. Together, these findings suggest that hyperacusis originates in the ipsilateral brainstem and midbrain rather than the peripheral auditory apparatus of patients with CRPS. Failure of processes that jointly modulate afferent auditory signalling and pain (eg, inhibitory influences stemming from the locus coeruleus) could contribute to ipsilateral hyperacusis in CRPS.

Spinal cord stimulator medullary compression-a very rare SCS complication and surgical treatment.

INTRODUCTION: The risk of spinal cord damage after Spinal Cord Stimulator (SCS) implant is a very rare event. In our case report, the patient was affected by a progressively worsening spinal stenosis due to SCS compression. CASE REPORT: The authors describe a progressive paraparesis in a 58-year-old woman with a long history of back pain and multiple spine surgeries. Computed tomography (CT) outlined vertebral canal stenosis corresponding to an electrode array implanted in T9. A posterior T8-T10 spinal cord decompression with explanation of the SCS device was performed and a partial neurological improvement was observed immediately postoperative. DISCUSSION: Spinal cord stimulation has been used since 1967 for the treatment of refractory chronic pain, particularly failed back surgery syndrome (FBSS) and complex regional pain syndrome (CRPS). Still, the mechanism underlying its function is not completely clear. Moreover, complications are mainly related to implant dysfunction and the risk of direct and indirect spinal cord compression is described as exceptional in the literature. Our aim is to describe the case SCS device spinal cord direct compression and its surgical treatment.

Spinal cord stimulation for neuropathic pain following traumatic spinal cord injury: a case report.

INTRODUCTION: Neuropathic pain is a common complication of spinal cord injury (SCI), and is notoriously difficult to adequately treat. Gunshot wounds (GSW) near the spinal cord may cause intractable chronic pain through spinal/nerve root transection, or reactive tissue formation resulting in nerve root compression from retained bullet fragments (RBF). CASE PRESENTATION: This case report describes a 30-year-old man with a T12 AIS B incomplete spinal cord injury with paraplegia secondary to multiple GSW who presented with severe bilateral lower extremity dysesthesias and muscle spasms. Symptoms failed to improve with oral antispasmodic medications. After being diagnosed with Complex regional pain syndrome (CRPS) type I secondary to an SCI via GSW, he underwent a spinal cord stimulator (SCS) trial, which improved his symptoms by greater than 80%. DISCUSSION: Neuropathic pain refractory to conservative treatment may benefit from SCS. Effects of therapy go beyond gate-theory in SCI patients, and may benefit patients at the cellular and molecular level. Our case demonstrates the effectiveness of SCS treatment in a patient who developed CRPS type 1 after GSW resulting in SCI.

Visual Sensitivity in Complex Regional Pain Syndrome and Fibromyalgia: An Online Study.

Perceptual anomalies can provide insights into underlying pathologies even when they are not the main symptom of many clinical conditions. Complex regional pain syndrome (CRPS) and fibromyalgia are chronic pain conditions associated with changes in the central nervous system, possibly leading to enhanced visual sensitivity. It is unclear whether this occurs more than for people with other types of pain. We examined visual sensitivity elicited by different stimuli and in daily life, through an online study of people with CRPS (n = 57), fibromyalgia (n = 74), other pain (n = 50), and no pain (n = 89). Respondents rated changes in pain, discomfort, or distress from viewing patterns with different spatial frequencies (lower-order visual processing), and reversible figures (bistable images; higher-order visual processing). We assessed visual sensitivity in daily life using the Leiden Visual Sensitivity Scale and Visual Discomfort Scale. Respondents with CRPS or fibromyalgia reported more visual discomfort than pain-related and pain-free controls while viewing striped patterns and a circle, with no effect of spatial frequency. They reported more pain while viewing a nonreversible square, but not reversible figures (Necker Cube, Duck/Rabbit). Finally, they reported more daily visual sensitivity than pain-related and pain-free controls. Suppressing visual cortical activity might benefit people with CRPS or fibromyalgia.

Risks of therapeutic versus prophylactic neurectomies.

INTRODUCTION: Neuralgia due to a peripheral nerve injury may result in chronic pain, requiring a therapeutic surgical neurectomy. Meanwhile, some neurectomies are performed prophylactically, such as during inguinal mesh removal. Outcomes and risks associated with neurectomies are largely unknown despite consensus panels recommending them. METHODS: All patients who underwent neurectomy 2013-2020 were analyzed. Data collection included demographics, preoperative symptoms, and postoperative outcomes. Indications for neurectomy were categorized as "therapeutic" if the patient had preoperative neuralgia or "prophylactic" if neurectomy was deemed necessary intra-operatively. RESULTS: 66 patients underwent 80 operations and a total of 122 neurectomies. On average, 1.5 neurectomies were performed per operation. Therapeutic neurectomies were performed in 42 (64%) patients and prophylactic in 34 (52%). The most commonly transected nerve was the ilioinguinal nerve. Average preoperative pain score was 5.8/10. On paired analysis, there was a significant reduction in pain after prophylactic neurectomy (2.5 points, p = 0.002) but not after therapeutic neurectomy. None of the nerves transected prophylactically had postoperative neuralgia, whereas 35% of the nerves transected therapeutically resulted in persistent or recurrent neuralgia (p < 0.001). To treat this, 21% required only nerve blocks and 9% required ablation or reoperative neurectomy. Three patients had complex regional pain syndrome (CRPS), a severe complication; all three were diagnosed with chronic pain syndrome pre-operatively. DISCUSSION: We demonstrate that prophylactic neurectomy is largely safe. In contrast, a therapeutic neurectomy had a 35% risk of persistent or recurrent neuralgia, 9% required additional ablative or reoperative neurectomy. Three patients advanced from chronic pain syndrome to CRPS. We recommend the decision to perform a neurectomy be judicious and selective, especially in patients with known chronic pain syndrome. Prior to planning surgical neurectomy, other less invasive modalities should be exhausted and patients should be aware of its risks.

Co-morbidity between trigeminal autonomic cephalalgias and complex regional pain syndrome: Two case reports.

BACKGROUND: Trigeminal autonomic cephalalgias and complex regional pain syndrome are rare conditions, and their co-occurrence has not been reported previously.Clinical findings: In two patients, ipsilateral trigeminal autonomic cephalalgias developed after the onset of upper limb complex regional pain syndrome. Hyperalgesia to thermal and mechanical stimuli extended beyond the affected limb to encompass the ipsilateral forehead, and was accompanied by ipsilateral hyperacusis and photophobia. In addition, examination of the painful limb and bright light appeared to aggravate symptoms of trigeminal autonomic cephalalgias. Detailed examination of the association between facial and upper limb pain indicated that both sources of pain cycled together. Furthermore, in one case, stellate ganglion blockade inhibited pain for an extended period not only in the affected limb but also the face. CONCLUSIONS: These findings suggest some overlap in the pathophysiology of complex regional pain syndrome and trigeminal autonomic cephalalgias. Specifically, central sensitization and/or disruption of inhibitory pain modulation on the affected side of the body in complex regional pain syndrome might trigger ipsilateral cranial symptoms and increase vulnerability to trigeminal autonomic cephalalgias.

Attention upturned: Bias toward and away from the affected side of the body and near space in a case of complex regional pain syndrome.

People with Complex Regional Pain Syndrome (CRPS) following limb injury can show neuropsychological symptoms in the absence of observable brain pathologies. These can include sensory changes, distorted body representation, and inattention to their affected limb and its surrounding space, resembling post-stroke hemispatial neglect. The precise nature and mechanisms of these neuropsychological symptoms are unclear, however insights could be gained by testing for dissociations and associations that have been observed in stroke patients. Drawing from clinical and experimental methods for investigating spatial attention bias and related symptoms in stroke patients, we conducted a detailed investigation of neuropsychological symptoms in a woman with CRPS of her left arm who initially presented to us with pronounced inattention to her affected side. The patient showed visual and tactile neglect and extinction on her affected side on confrontation tests, but no attention deficits on "bedside" tests of neglect. On sensitive computer-based measures, attention biases were found in the patient's body and near space (in Temporal Order Judgements), but not far or imagined space (on the Greyscales task and Mental Number Line Bisection). Unique to the current literature, the patient showed a reversal in her Temporal Order Judgement bias across time, from inattention (first and second session) to hyperattention (third session) to her affected side. In contrast, pain and self-reported body representation distortion were similar across the three sessions. The patient had reduced central and peripheral visual acuity, however these deficits were near symmetrical and therefore could not explain her performance on the visual attention tasks. Given that spatial attention bias has been linked to imbalance in relative activation of the two cerebral hemispheres, we administered a Global-Local processing task to test for hemispheric asymmetry. This revealed no difference in global compared to local interference refuting any hemispheric imbalance. Instead, the patient showed impaired performance (compared to controls) on incongruent trials regardless of trial type, consistent with executive impairment. We conclude that spatial attention bias in CRPS can generalize across different sensory modalities and extend beyond the affected limb to the external space around it, independent of any low-level sensory disturbances. This bias is not necessarily directed away from the affected side or stable over time. People with CRPS can also demonstrate more generalized neuropsychological changes in sensory and executive functions. Our observations refute several existing theories about the mechanisms of attention bias in CRPS, and their relationship to pain, and have potential implications for treatment.

Validation of the Bath CRPS Body Perception Disturbance Scale.

The Bath Complex Regional Pain Syndrome Body Perception Disturbance Scale ("B-CRPS-BPDS") measures alterations in body perception. We assessed its internal consistency, known group validity, construct validity, and associations with demographic and clinical characteristics. We also evaluated changes in, and baseline predictors of B-CRPS-BPDS scores at follow-up. We included people with CRPS (N = 114) and pain-free controls (N = 69). People with CRPS obtained higher scores than pain-free controls on all B-CRPS-BPDS items, except the item on attention. Because this item also had an insufficient corrected item-total correlation, we propose a revised B-CRPS-BPDS (r-B-CRPS-BPDS) excluding this item. The internal consistency of the r-B-CRPS-BPDS was good. The r-B-CRPS-BPDS showed a large positive relationship with "motor neglect-like symptoms", indicating good construct validity. The r-B-CRPS-BPDS showed positive relationships with pain intensity, fear of movement, depression, and upper limb disability. There were no independent relationships with handedness, affected side, affected limb, disease duration, CRPS severity score, tension, anger, fatigue, confusion, and vigour. Finally, r-B-CRPS-BPDS scores did not consistently change over time. Our results demonstrate the utility of the r-B-CRPS-BPDS for measuring body perception disturbances in CRPS. PERSPECTIVE: This article evaluates the validity of the Bath Complex Regional Pain Syndrome Body Perception Disturbance Scale ("B-CRPS-BPDS") in CRPS, and assesses relationships with demographic and clinical variables. The proposed revised B-CRPS-BPDS appears to be a valid measure of body perception disturbances in CRPS.

Neurological Causes of Chest Pain.

PURPOSE OF REVIEW: Chest pain is a very common presenting complaint among patients in the hospital, a large proportion of whom have non-cardiac chest pain (NCCP). Neurological causes of NCCP have not been previously reviewed although several causes have been identified. RECENT FINDINGS: Chest pain has been reported as a symptom of multiple neurological conditions such as migraine, epilepsy, and multiple sclerosis, with varying clinical presentations. The affected patients are often not formally diagnosed for long periods of time due to difficulties in recognizing the symptoms as part of neurological disease processes. This paper will briefly summarize well-known etiologies of chest pain and, then, review neurological causes of NCCP, providing an overview of current literature and possible pathophysiologic mechanisms.

Associated Neurotrophic Keratopathy in Complex Regional Pain Syndrome.

PURPOSE: To report a case of neurotrophic keratopathy (NK) in a patient with complex regional pain syndrome (CRPS) with ipsilateral facial involvement. METHODS: Case report. RESULTS: An 18-year old woman with a 5-year history of CRPS type I, a systemic disorder with a neuropathic component with associated limb and right facial involvement, presented with an insidious onset of blurred vision and pain in the right eye. Ocular examination revealed decreased corneal sensation, as measured by Cochet-Bonnet testing, associated with recurrent epithelial defects and whorl-like superficial corneal epitheliopathy. NK was suspected and confirmed by in vivo confocal microscopy (IVCM), which revealed rarefaction of the subbasal nerve plexus in the affected eye. To enhance corneal nerve health, plasma rich in growth factors drops were used. Persistence of NK prompted a superficial keratectomy with placement of an amniotic membrane graft and a course of cenegermin 0.002% (Oxervate; Dompé Farmaceutici SpA, Italy) in the postoperative period. This combination therapy resulted in successful epithelial closure and vision improvement after 8 weeks of therapy with no recurrence of disease for 11 months. Importantly, at that final visit, IVCM demonstrated growth of corneal nerves for the first time in this patient. CONCLUSIONS: This is the first case report of NK occurring in the context of CRPS, a neuropathy with ipsilateral facial pain involvement. IVCM was important in the diagnosis of NK, which responded successfully to ocular surface treatments focused on nerve health stimulation that ultimately resulted in corneal nerve growth.

Abnormal neuroinflammation in fibromyalgia and CRPS using [11C]-(R)-PK11195 PET.

PURPOSE: Fibromyalgia (FM) and complex regional pain syndrome (CRPS) share many pathological mechanisms related to chronic pain and neuroinflammation, which may contribute to the multifactorial pathological mechanisms in both FM and CRPS. The aim of this study was to assess neuroinflammation in FM patients compared with that in patients with CRPS and healthy controls. METHODS: Neuroinflammation was measured as the distribution volume ratio (DVR) of [11C]-(R)-PK11195 positron emission tomography (PET) in 12 FM patients, 11 patients with CRPS and 15 healthy controls. RESULTS: Neuroinflammation in FM patients was significantly higher in the left pre (primary motor cortex) and post (primary somatosensory cortex) central gyri (p < 0.001), right postcentral gyrus (p < 0.005), left superior parietal and superior frontal gyri (p < 0.005), left precuneus (p < 0.01), and left medial frontal gyrus (p = 0.036) compared with healthy controls. Furthermore, the DVR of [11C]-(R)-PK11195 in FM patients demonstrated decreased neuroinflammation in the medulla (p < 0.005), left superior temporal gyrus (p < 0.005), and left amygdala (p = 0.020) compared with healthy controls. CONCLUSIONS: To the authors' knowledge, this report is the first to describe abnormal neuroinflammation levels in the brains of FM patients compared with that in patients with CRPS using [11C]-(R)-PK11195 PET. The results suggested that abnormal neuroinflammation can be an important pathological factor in FM. In addition, the identification of common and different critical regions related to abnormal neuroinflammation in FM, compared with patients with CRPS and healthy controls, may contribute to improved diagnosis and the development of effective medical treatment for patients with FM.

Novel Presentation of Pediatric Complex Regional Pain Syndrome with Concurrent Chromhidrosis: A Case Report.

CASE: An 11-year-old female patient presented to our clinic with a low-grade lateral ankle sprain that was subsequently treated with a lace-up ankle brace. On the reintroduction of weight bearing, the patient developed recurrent ankle pain and symptoms consistent with complex regional pain syndrome (CRPS) Type 1. On physical examination, the patient was found to have a concurrent chromhidrosis in the injured area, which is a novel presentation of CRPS. CONCLUSION: Patients with CRPS found to have superficial skin discoloration should be evaluated further to investigate for chromhidrosis. Early diagnosis can improve the treatment of CRPS and allow for appropriate management of varying manifestations, such as chromhidrosis.

Effectiveness of perampanel in managing chronic pain caused by the complex regional pain syndrome: A case report.

RATIONALE: The α-amino-3-hydroxy-5-methy-4-isoxazole propionate (AMPA) receptor plays a critical role in the development and persistence of pain, and AMPA receptor antagonists are considered possible therapeutic targets for controlling pain. This report describes a patient with complex regional pain syndrome (CRPS) type I in the right lower leg and foot who responded well to perampanel, an AMPA receptor antagonist, for managing the chronic pain. PATIENT CONCERN: A 61-year-old woman complained of pain in her right lower leg and foot over a period of 7 year (numeric rating scale: 8) due to CRPS type I. DIAGNOSIS: CRPS type 1. INTERVENTIONS: Despite the combination of 300 mg pregabalin, 225 mg/1950 mg tramadol/acetaminophen, and 10 mg nortriptyline per day, her right lower leg and foot were nearly disabled due to the severity of the pain. High-dose prednisolone was found to be ineffective. Then, perampanel (4 mg; 2 mg twice) was administered to this patient daily. OUTCOMES: The day after treatment with perampanel, her pain completely disappeared. Additionally, at day 7 and 1 month follow-up, she reported no pain in the right lower leg and foot. Moreover, no adverse effects were reported after the application of perampanel. LESSONS: These results suggest that perampanel may potentially be used to treat centralized pain.

Photophobia in complex regional pain syndrome: visual discomfort is greater on the affected than unaffected side.

ABSTRACT: In complex regional pain syndrome (CRPS), hyperalgesia encompasses uninjured sites on the ipsilateral side of the body and may also include the special senses because auditory discomfort often is greater on the CRPS-affected side. To determine whether this hemilateral hyperalgesia involves the visual system, the discomfort threshold to a light-source that increased in intensity at 100 lux/second from 500 to 3600 lux was investigated for each eye, and the nasal and temporal half of each visual field, in 33 patients with CRPS and 21 pain-free controls. Recent headache history was reviewed and, in patients with CRPS, sensitivity to mechanical and thermal stimuli was assessed in all 4 limbs and on each side of the forehead. In addition, the pupils were photographed in dim and bright light. The visual discomfort threshold was lower in patients than controls and was lower on the CRPS-affected than unaffected side (P < 0.001), indicating photophobia. Visual discomfort was unrelated to pupil diameter. Headache frequency was greater in CRPS patients than controls, and unilateral headaches were more likely to be on the CRPS-affected than contralateral side. Similarly, mechanical and thermal hyperalgesia was greater in the CRPS-affected than contralateral limb and was greater ipsilateral than contralateral to CRPS in the forehead and nonsymptomatic limbs. Ipsilateral photophobia was associated with mechanical and thermal hyperalgesia in the ipsilateral forehead but not the CRPS-affected limb. Together, these findings suggest that aberrant processing of nociceptive input in the ipsilateral trigeminal-medullary region of the brainstem contributes to visual discomfort in CRPS.