Table 2.
Original publications on pain in neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein-antibody-associated disease (MOGAD) (listed in chronological order).
| References | Patient sample | Portion of AQP4-IgG seropositive patients | Pain and QoL assessment | Imaging data | Pain type | Pain medication | Main findings |
|---|---|---|---|---|---|---|---|
| Kanamori et al. (18) | 42 NMOSD vs. 51 MS | 35/42 | SF-BPI SF-36 |
N.A. | N.A. | N.A. | First study on pain in NMOSD: Pain in NMOSD is more frequent and severe than in MS and has a severe impact on the patients' QoL |
| Qian et al. (27) | 29 NMOSD vs. 66 MS | 24/29 | MPQ 10-point NRS Interview SF-36 |
Spinal cord MRI | Retroorbital pain Dysesthetic pain Girdle pain Lhermitte's sign Painful tonic spasms |
Tricyclic antidepressants Duloxetine Gabapentin Pregabalin Carbamazepine Lamotrigine Phenytoin Sodium valproate Baclofen Cyclobenzaprine Tizanidine Fentanyl citrate Hydrocodone Hydromorphone Methadone Oxycodone Hydromorphone |
First study mentioning specific pain syndromes, including spinal cord MRI and examining medication use: Pain in NMOSD is more frequent and severe than in MS, even after controlling for disability and number of involved spinal cord segments. Pain in NMOSD appears insufficiently controlled by pharmacological interventions |
| Kim et al. (29) | 40 NMOSD vs. 35 MS vs. 42 iATM | 34/40 | N.A. | Spinal cord MRI | Painful tonic spasms | Carbamazepine Gabapentin Phenytoin |
First study on PTS in NMOSD: PTS are a common and relatively specific myelitis-related symptom in NMOSD. PTS most commonly occur during recovery from the first myelitis episode |
| Usmani et al. (31) | 57 NMOSD | 1/57 | Clinical history | Spinal cord MRI | Painful tonic spasms | Carbamazepine | 14% of NMOSD patients had documented typical tonic spasms |
| Elsone et al. (52) | 45 NMOSD | 45/45 | Clinical history | Spinal cord MRI | Neuropathic pruritus | N.A. | First study on neuropathic pruritus in NMOSD: Neuropathic pruritus seems to be a common but underrecognized symptom of myelitis associated with NMOSD |
| Pellkofer et al. (28) | 11 NMOSD vs. 11 HC | 11/11 | Interview DN4 NRS QST |
MRI | Neuropathic pain | N.A. | First study on NP in NMOSD, evaluating endocannabinoid levels in the serum and somatosensory abnormalities by QST: A total of 91% of the patients suffered from NP within the previous 3 months and 72% reported ongoing pain and decreased QoL at the time of assessment. Plasma levels of 2-AG were higher in NMOSD patients than in HC, suggesting its relevance for central sensitization. QST revealed pronounced mechanical and thermal sensory loss, strongly correlated to ongoing pain suggesting the presence of deafferentiation-induced pain |
| Zhao et al. (26) | 50 NMOSD | 41/50 | DN4 BPI SF-36 |
MRI reports | Neuropathic pain | Amitriptyline Duloxetine Gabapentin Pregabalin Carbamazepine Lamotrigine Baclofen Cannabinoids Paracetamol Opiates |
Specific exploration of NP and its effect on the QoL. NP was identified in 62% of patients, affecting ADLs. Pain was associated with significant reduction in the SF-36 mental composite score |
| Mutch et al. (50) | 15 NMOSD | 9/15 | Semistructured interview | N.A. | Neuropathic pain | N.A. | First qualitative study to explore QoL, including pain in NMOSD: NMOSD is a difficult condition to live with due to the unpredictability of relapses and severe disability of visual or spinal symptoms. Poor vision, reduced mobility, bladder dysfunction, and pain affected participants' independence and experience of living with NMOSD |
| Carnero Contentti et al. (30) | 15 NMOSD | 15/15 | Clinical history | MRI | Painful tonic spasms | Carbamazepine Gabapentin |
PTS occur frequently in patients with NMOSD. PTS generally appear a month after a myelitis attack and are associated with extensive cervicothoracic lesions in MRI |
| Kong et al. (51) | 44 NMOSD | 29/44 | BPI HADS SF-36 |
N.A: | Pain (not specified) | Codeine Ibuprofen Paracetamol Amitriptyline Duloxetine Diazepam Clonazepam Gabapentin Pregabalin Carbamazepine Oxcarbazepine Baclofen |
Pain correlated strongly with quality of life SF-36 physical composite score. Depression highly correlated with pain severity. Pain severity was the most important factor for QoL |
| Eaneff et al. (25) | 522 self-reported NMOSD | N.A. | PatientsLikeMe online questionnaire | N.A. | Pain (not specified) | Duloxetine Gabapentin Pregabalin Baclofen |
Moderate to severe fatigue, pain, stiffness, and spasticity limit activities of over 50% of NMOSD patients |
| Tackley et al. (53) | 76 NMOSD | 76/76 | BPI | MRI | Neuropathic pain | N.A. | Persistent, thoracic cord lesions in AQP4-Ab positive NMOSD is associated with high postmyelitis chronic pain scores, irrespective of number of myelitis relapses, lesion length, and lesion burden |
| Asseyer et al. (2) | 35 NMOSD vs. 14 MOGAD | 29/35 | painDETECT MPQ SF-36 BDI-II |
MRI | Neuropathic pain Headache/neck pain Musculoskeletal pain Spasticity |
NSAID Antidepressants Anticonvulsants Opioids |
First study exploring pain in MOGAD: Pain is a frequent symptom of patients with MOGAD and has a severe impact on the patients' QoL in NMOSD and MOGAD. Pain is insufficiently alleviated by medication |
| Liu et al. (32) | 230 NMOSD | 181/230 | Medical records Prospective interviews |
MRI | Painful tonic spasms | Carbamazepine Oxcarbazepine Gabapentin Pregabalin Baclofen |
22.6% of NMOSD patients experience PTS. Patients with NMOSD and PTS have a higher age at disease onset, higher ARR, and a tendency to experience pruritus. Sodium channel blocking antiepileptic drugs like carbamazepine and oxcarbazepine have higher efficacy than gabapentin in the treatment of PTS |
| Asseyer et al. (54) | 129 MOGAD | No NMOSD | Medical records | MRI | Optic neuritis related headache and orbital/periorbital pain | N.A. | First study on severe headache preceding visual loss in MOG-Ab-related optic neuritis. Florid intraorbital and perioptic inflammation was likely to involve meninges and nociceptive fibers |
| Hyun et al. (49) | 252 NNOSD vs. 248 MS | 91/99 who completed PainDetect | PainDetect SF-BPI BDI-II FSS |
N.A. | Pain (not specified) Neuropathic pain |
N.A. | 60% of the NMOSD patients and 34% of the MS patients suffered from current pain. Neuropathic pain was more severe and pain-related interference in daily life was greater in NMOSD patients than in MS patients |
| Mealy et al. (55) | 22 NMOSD | 22/22 | Self-reported NP attributable to an inflammatory spinal cord lesion NRS |
Details n.a. | Neuropathic pain | Antidepressants Anticonvulsants Opioids |
First randomized single-blind, sham-controlled trial in NMOSD patients with central neuropathic pain using Scrambler therapy. The median baseline NRS decreased after 10 days of treatment, whereas the median NRS score did not significantly decrease in the sham arm |
| Wang et al. (56) | 38 NMOSD | 38/38 | BPI | MRI | Neuropathic pain, but not clearly specified | N.A. | First investigation of subcortical structural abnormalities in female NMOSD patients with NP shows significantly smaller hippocampus and pallidum volumes in the patients with NP compared to patients without NP and a significant negative correlation between pain intensity and volumes of the accumbens nucleus and thalamus in patients with NP |
2-AG, 2-arachidonoylglycerol; ADL, activities of daily living; AQP4-IgG, aquaporin 4 immunoglobulin G; ARR, annualized relapse rate; BDI-II, Beck Depression Inventory II; BPI, Brief Pain Inventory; DN4, Douleur neuropathique 4; FSS, Fatigue Severity Scale; HADS, Hospital Anxiety and Depression Scale; HC, healthy control; iATM, idiopathic acute transverse myelitis; MOG-Ab, myelin oligodendrocyte glycoprotein antibody; MOGAD, myelin oligodendrocyte glycoprotein-associated disease; MPQ, McGill Pain Questionnaire; MRI, magnet resonance imaging; MS, multiple sclerosis; NMOSD, neuromyelitis optica spectrum disorders; NP, neuropathic pain; NRS, numeric rating scale; PTS, painful tonic spasms; QoL, quality of life; QST, quantitative sensory testing; SF-36, 36 item short form health survey; SF-BPI, short form Brief Pain Inventory.