Genetic implications in quality palliative care and preventing opioid crisis in cancer-related pain management.

The prevalence of cancer-related pain is 64% among patients with metastatic, advanced, or terminal cancer, 59% among patients undergoing anticancer treatment, and 33% among patients who completed curative treatment. According to the World Health Organization cancer pain relief guidelines, opioid analgesics are the mainstay analgesic therapy in addition to conventional first-step analgesics, such as non-steroidal anti-inflammatory drugs and acetaminophen. The indications for strong opioids have recently been expanded to include mild-to-moderate pain in addition to moderate-to-severe pain. The U.S. Centers for Disease Control and Prevention guidelines emphasize that realistic expectations should be weighed against potential serious harm from opioids, rather than relying on the unrealized long-term benefits of these drugs. Therefore, treatment strategies for both cancer-related chronic or acute pain have been unfortunately deviated from opioid analgesics. The barriers hindering adequate cancer-related pain management with opioid analgesics are related to the inadequate knowledge of opioid analgesics (e.g., effective dose, adverse effects, and likelihood of addiction or tolerance). To achieve adequate opioid availability, these barriers should be overcome in a clinically suitable manner. Genetic assessments could play an important role in overcoming challenges in opioid management. To balance the improvement in opioid availability and the prevention of opioid misuse and addiction, the following two considerations concerning opioids and genetic polymorphisms warrant attention: (A) pain severity, opioid sensitivity, and opioid tolerance; and (B) vulnerability to opioid dependence and addiction.

Prefectural Adequacy of Opioid Availability for Cancer Pain and Its Determinants in Japan: A Preliminary Study.

INTRODUCTION: Opioid analgesics are the mainstay of cancer pain management. The annual opioid consumption globally indicates adequate opioid availability and the quality of palliative care. We investigated the current situation regarding the adequacy of opioid availability in individual prefectures in Japan and explored the determinants of adequacy. METHODS: We analyzed nationwide databases open to public inspection depicting the current Japanese healthcare situation. Opioid consumption for cancer pain was estimated from oxycodone and morphine data in the nationwide database. On the basis of the World Health Organization recommendations, we calculated adequacy based on the annual cancer deaths in each prefecture in 2013 and 2015. We investigated the associations between adequacy and either outpatient medical expenditure for hypertension and diabetes as a proxy of primary care practice or ratios of these risk holders in community. Outpatient medical expenditures for musculoskeletal disorders and neoplasms were also investigated. RESULTS: The nationwide adequacy of opioid availability was approximately 75%. The largest gaps in adequacy between prefectures were more than 65%. The adequacy correlated with expenditure but not local volumes of hypertension and diabetes in both years. The other two expenditures did not relate to opioid availability. CONCLUSIONS: Although precise data are required, our preliminary findings indicate that primary care practice is the key regulator of adequate opioid availability. Opioid adequacy in Japan is thus delayed in matching the global standard, and gaps in opioid adequacy among prefectures should be bridged rapidly to expand universal access to effective palliative care and cancer pain relief.

Use of three-dimensional printing of a lumbar skeletal model for intrathecal administration of nusinersen: a brief technical report.

Spinal muscular atrophy (SMA) is an autosomal recessive hereditary neurodegenerative disease causing progressive muscle atrophy, weakness and kyphoscoliosis. Nusinersen is a therapeutic agent for SMA that should be administered intrathecally. However, due to severe kyphoscoliosis, lumbar puncture can be challenging. Here, we present our experience of intrathecal administration of nusinersen in an SMA patient with severe kyphoscoliosis using a life-size three-dimensional printing (3D) skeletal model created with 3D printer. With this strategy, we were able to rapidly and safely perform the lumbar puncture.

Adiponectin receptor 1 gene is potentially associated with severity of postoperative pain but not cancer pain.

Adiponectin is an adipose tissue-derived cytokine that exerts its antiinflammatory effects by binding to 2 adiponectin receptors, adiponectin receptor 1 (ADIPOR1) and adiponectin receptor 2 (ADIPOR2). However, the role of these adiponectin receptors on inflammatory pain remains unclear. We investigated the association between single nucleotide polymorphisms (SNPs) of these genes and inflammatory pain, such as postoperative pain and cancer pain.We analyzed 17 SNPs of the ADIPOR1 gene and 27 SNPs of the ADIPOR2 gene in 56 adult patients with postlaparotomy pain. We compared these genotypes with pain intensity and opioid consumption, adjusting for multiple testing. We analyzed the genotypes of 88 patients with cancer pain and examined the association of the relevant SNP(s) with pain intensity and opioid consumption.One variant of the ADIPOR1 gene (rs12045862) showed significant association with postoperative pain intensity; patients with minor allele homozygote (n = 7) demonstrated significantly worse pain intensity than that of combined patient group exhibiting major allele homozygote or the heterozygote (n = 49; Mann-Whitney test, P < .00002), although their opioid consumptions were comparable. Cancer pain intensity between minor allele homozygote patients (n = 7) and other 2 genotype patients (n = 81) were comparable.The rs12045862 SNP of the ADIPOR1 gene was associated with postoperative pain but not cancer pain. This might result from functional alteration of the ADIPOR1 signalling pathways, which influence the inflammatory process. ADIPOR1 may be a novel potential target for developing analgesics of postoperative pain.

A Novel Technique Using Magnetic Resonance Imaging in the Supine and Prone Positions for Diagnosing Lumbar Adhesive Arachnoiditis: A Preliminary Study.

BACKGROUND: Lumbar adhesive arachnoiditis is a debilitating neuropathic condition and is difficult to diagnose owing to lack of definitive diagnostic criteria. By focusing on the intrathecal mobility of nerve roots, we assessed whether useful diagnostic criteria could be established using MRI. METHODS: Seventeen patients with a high risk for lumbar adhesive arachnoiditis and 18 no-risk patients with chronic low back pain and/or leg pain participated in this study. The patients underwent MRI in both the supine and prone positions. Eleven axial T2-weighted images between the L2 and L5/S levels were obtained, and the proportion of the low-intensity area in the dorsal half to the total low-intensity area in the dural sac was calculated for each axial view. RESULTS: At some lumbar levels, the low-intensity area in the dorsal half of the dural sac was relatively larger in patients with a high risk for lumbar adhesive arachnoiditis than in the no-risk patients. In the no-risk group, the proportion of the low-intensity area in the dorsal half in the supine position was significantly higher than that in the prone position at all lumbar levels. However, in the high-risk group, at some levels, the proportions were not significantly different in the dorsal half of the dural sac between the supine and prone positions. CONCLUSION: In patients with a known risk for lumbar adhesive arachnoiditis, nerve roots lose their potential to migrate in the dural sac in the gravitational force direction on MRI.

Resistin Is a Novel Marker for Postoperative Pain Intensity.

BACKGROUND: Pro- and anti-inflammatory cytokines (adipokines) associated with adipose tissue can modulate inflammatory processes and lead to systemic inflammatory conditions such as metabolic syndrome. In the present pilot study, we investigated 3 major adipokines (leptin, adiponectin, and resistin) and 2 nonspecific proinflammatory cytokines (tumor necrosis factor α and interleukin-6) with regard to their association with postoperative pain intensity. METHODS: We analyzed a total of 45 single-nucleotide polymorphisms of the adipokines in 57 patients with postlaparotomy pain. We adjusted for multiple testing to reduce the chance of false-positive results by controlling the false discovery rate. Serum levels of the adipokines and proinflammatory cytokines were measured in another 36 patients undergoing laparotomy. A stepwise multiple linear regression analysis using these measurements and opioid dosages as independent variables was performed to explore the factors associated with postoperative pain. RESULTS: Only 1 variant of the resistin gene (rs3745367) demonstrated a significant association with postoperative pain (P < .002). Patients exhibiting homozygosity for the minor alleles (n = 7; numerical rating scale [NRS], 2.3 ± 1.3) demonstrated lower pain intensity compared with those exhibiting homozygosity for the major alleles (n = 29; NRS, 3.8 ± 1.0; P = .004) and heterozygosity for the minor alleles (n = 21; NRS, 4.2 ± 0.8; P < .001). Only serum resistin levels showed a positive association with postoperative pain. CONCLUSIONS: A genetic variant of resistin and serum resistin levels were associated with postoperative pain intensity, while other adipokines and cytokines exhibit no such association. Resistin can alter the inflammatory responses in postoperative wounds, although it could be a determinant factor that is independent of inflammatory processes. Resistin may be a novel marker for postoperative pain intensity.

Characteristics of Locomotive Syndrome in Japanese Patients with Chronic Pain and Results of a Path Analysis Confirming the Relevance of a Vicious Cycle Involving Locomotive Syndrome, Musculoskeletal Pain, and Its Psychological Factors.

INTRODUCTION: The current aging population has a major impact on public health. Locomotive syndrome (LS) is a condition that carries a high risk for developing systemic musculoskeletal disability. METHODS: Participants were patients with chronic pain (n = 415) who were examined at the Japanese multidisciplinary pain centers of the research consortium. They completed the 25-question geriatric locomotive function scale (GLFS-25; LS screening tool), an 11-point numerical rating scale (NRS) of pain intensity and its psychological distresses, health-related quality of life (HRQOL) questionnaire, and a survey of exercise habits. A multifaceted analysis of the relevance of the pain, psychological distresses, and LS were conducted using SPSS and AMOS software. RESULTS: 337 patients (81.2%) were found to have LS. The final model of a multifaceted analysis demonstrated good fitness for the "vicious cycle" model among the results of LS, pain intensity, impairment of self-efficacy, and depression; these parameters independently impaired HRQOL. Anxiety related to falling (GLFS-25) and exercise habits affected the model. CONCLUSIONS: These findings indicate LS, LS-related pain, and psychological distress create a vicious cycle, resulting in the impairment of HRQOL. Treatment strategies for LS should inclusively focus on musculoskeletal disorders, pain, and pain-related psychological factors.

Gamma-aminobutyric acid transaminase genetic polymorphism is a candidate locus for responsiveness to opioid analgesics in patients with cancer pain: An exploratory study.

AIM: Cancer pain impairs not only physical functions but also social functions and roles. Consequently, the overall health-related quality of life of patients with cancer pain deteriorates. Opioid analgesics are recommended for treating moderate to strong cancer pain. Advances in human genome research have fueled a growing interest to understand individual differences in responsiveness to opioid analgesics. This study aimed to explore and identify novel loci for genes predisposing an individual to opioid analgesic responsiveness. METHODS: A total of 71 cancer patients rated their pain on an 11-point numerical rating scale twice before and after increasing opioid analgesics. A genomewide association study focusing on single nucleotide polymorphisms (SNPs) was conducted to associate pain decrease with increased dosage of opioid analgesics based on weight (ie, responsiveness to opioid analgesics). A genomewide significance (P < 5E-8) was set for multiplicity of analyses to control for false positives. RESULTS: Two SNPs passed the genomewide threshold for significance. One exonic SNP (rs1641025) was located in the ABAT [4-aminobutyrate aminotransaminase (GABA transaminase)] gene on chromosome 16. The other SNP (rs12494691) was located on chromosome 3, which was not associated with any known genes. These SNPs were not associated with opioid-related adverse effects. CONCLUSIONS: Our results preliminarily suggest that both SNPs might be potential candidate loci for responsiveness to opioid analgesics, and GABA transaminase might be a possible target for developing adjuvant pharmacotherapy with opioid analgesics in adjuvant pharmacotherapy. Our results should be validated in a large-scale study with a larger sample size.

Ischemic Ulcer Pain Is Both Nociceptive and Neuropathic Pain Based on a Discriminant Function Analysis Using the McGill Pain Questionnaire.

The McGill Pain Questionnaire (MPQ) is composed of 78 words reflecting the mechanisms underlying chronic pain conditions. Ischemic ulcer pain is generally regarded as a nociceptive and inflammatory pain condition. However, it is sometimes refractory to nonsteroidal anti-inflammatory drug (NSAID) and opioid treatment. We categorized ischemic pain into nociceptive/inflammatory pain (NocP) or neuropathic pain (NeP), on the basis of patients' descriptions of their pain using the MPQ. We investigated pain characteristics of 365 patients with NeP and 124 with NocP using the 78 words of the MPQ. We thereby developed a discriminant function, which efficiently discriminates descriptions of NocP from those of NeP. We applied this function to 18 ischemic pain patients (before and after peripheral revascularization) and categorized their pain as either NocP or NeP. The discriminant probability of the function was 72.8% (P <.05), suggesting relatively accurate discrimination of NocP from NeP. Among the 78 words, only "annoying" was not utilized for the function. On the basis of this function, 9 of the 18 ischemic pain patients' complaints were classified as NeP. Ten patients received revascularization and after revascularization, 7 of 10 patients' complaints were still NeP. Our results suggest that ischemic ulcer pain should be regarded as a mixed pain condition composed of both NocP and NeP and that it might be treated with medications for NeP (e.g., pregabalin, duloxetine) in combination with NSAIDs and opioids.

Donepezil, an Acetylcholinesterase Inhibitor, Can Attenuate Gabapentinoid-Induced Somnolence in Patients with Neuropathic Pain: A Retrospective Chart Review.

Donepezil, an oral acetylcholinesterase inhibitor, is used to treat Alzheimer's disease and reportedly attenuates opioid-induced sedation in patients with cancer pain. Neuropathic pain is often treated with gabapentinoids (pregabalin, gabapentin), but gabapentinoid-induced somnolence sometimes prevents patients from using these agents. We conducted a retrospective chart review of patients with neuropathic pain to examine whether donepezil is useful for gabapentinoid-induced somnolence. We investigated pain severity in 13 patients before and after taking gabapentinoids and donepezil, the degree of gabapentinoid-induced somnolence before and after starting donepezil, and gabapentinoid dose escalation after taking donepezil. Donepezil was started at 3-5 mg/day upon experiencing gabapentinoid-induced somnolence. Likert-scale scores for somnolence (0 = no somnolence; 4 = severe somnolence with stumbling) improved significantly after starting donepezil (before: 2.3 ± 0.9, after: 0.5 ± 0.7; Wilcoxon's signed-rank test, P < .05), resulting in gabapentinoid dose escalation (before: 796.2 ± 564.3 mg, after: 1409.6 ± 526.9 mg; P < .05), which significantly decreased pain intensity (before: 7.4 ± 1.2, after: 5.0 ± 1.3; P < .05). Donepezil could be an alternative to psychostimulants for gabapentinoid-induced somnolence. The analgesic effect of gabapentinoids remained uncompromised by donepezil, which could enhance the dose-dependent analgesic effect of gabapentinoids.

Development of the Japanese Version of the Leeds Assessment of the Neuropathic Symptoms and Signs Pain Scale: Diagnostic Utility in a Clinical Setting.

OBJECTIVE: We aimed to assess the diagnostic utility of the linguistically validated Japanese version of the Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale (LANSS-J) as a screening tool for neuropathic pain in the clinical setting. METHODS: Patients with neuropathic pain or nociceptive pain who were 20 to 85 years of age were included. Sensitivity and specificity using the original cutoff value of 12 were assessed to evaluate the diagnostic utility of the LANSS-J. Sensitivity and specificity with possible cutoff values were calculated, along with area under the receiver operating characteristic curve. We then evaluated agreement regarding assessment of the LANSS-J by two investigators. We used the intraclass correlation coefficient (ICC) for the total score and Cohen's kappa coefficient for each item. RESULTS: Data for patients with neuropathic pain (n = 30) and those with nociceptive pain (n = 29) were analyzed. With a cutoff of 12, the sensitivity was 63.3% (19/30) and the specificity 93.1% (27/29). Sensitivity improved substantially with a cutoff of ≤ 11 (≥ 83.3%, 25/30). High specificity (93.1%, 27/29) was sustained with a cutoff of 9 to 12. The ICC for the total score was 0.85, indicating sufficient agreement. Kappa coefficients ranged from 0.68 to 0.84. CONCLUSIONS: The LANSS-J is a valid screening tool for detecting neuropathic pain. Our results suggest that employing the original cutoff value provides high specificity, although a lower cutoff value of 10 or 11 (with its high specificity maintained) may be more beneficial when pain attributed to neuropathic mechanisms is suspected in Japanese patients.

Dose of intraoperative remifentanil administration is independently associated with increase in the risk of postoperative nausea and vomiting in elective mastectomy under general anesthesia.

BACKGROUND: Postoperative nausea and vomiting (PONV) is one of the common complications in patients who have undergone surgery with general anesthesia. The association of intraoperative use of remifentanil with PONV has remained controversial. The aim of the current study was to determine the association of dose of intraoperative remifentanil administration with incidence of PONV. METHODS: The present study was a single-center retrospective observational study and included 423 female patients with American Society of Anesthesiologists physical status I or II who underwent elective mastectomy under general anesthesia between October 2011 and October 2012. The incidence of PONV within 3 days after the operation was prospectively assessed. The time-weighted average of remifentanil during the operation (twRem) was calculated. We used a multivariate regression model to assess the independent association of the twRem with the incidence of PONV. RESULTS: Among 423 patients, 129 patients (30.5%) had PONV during the study period. Remifentanil was administrated in 355 patients (83.9%). In the multivariate logistic regression model using categories of twRem, we found that increased twRem was independently associated with increase in the risk of PONV (P=.01). There was an independent association between twRem greater than 0.2 µg/kg per minute and increase in the risk of PONV. CONCLUSION: This retrospective observational study revealed a dose-dependent association between dose of intraoperative remifentanil administration and increase in the risk of PONV. Time-weighted average of remifentanil greater than 0.2 µg/kg per minute was independently associated with risk of PONV.

Relationship between Neuropathic Pain and Obesity.

Objectives. Overweight negatively affects musculoskeletal health; hence obesity is considered a risk factor for osteoarthritis and chronic low back pain. This was conducted to determine if obesity affects neuropathic pain, usually considered unrelated to the weight-load on the musculoskeletal system. Methods. Using a cut-off body mass index value of 25, 44 patients with neuropathic pain were grouped into a "high-BMI" group and a "normal-BMI" group. Results. The numeric rating scale of the high-BMI group was significantly higher than that of the normal-weight group (P < 0.05). The total NPSI scores were significantly higher (P < 0.01), and the paroxysmal pain and the negative symptoms were more serious in the high-BMI group than in the normal-BMI group. The high-BMI subjects also had significantly higher SF-MPQ scores (P < 0.05). However, both physical and mental health status on the SF-36 were comparable between the groups. Discussion. Neuropathic pain that did not arise from musculoskeletal damage was higher in the high-BMI patients. Paroxysmal pain was more severe, suggesting that neural damage might be aggravated by obesity-associated inflammation. These findings should have needed to be confirmed in future studies.

Poor efficacy of the phosphorylated high-molecular-weight neurofilament heavy subunit serum level, a biomarker of axonal damage, as a marker of chemotherapy-induced peripheral neuropathy.

The phosphorylated form of the high-molecular-weight neurofilament heavy subunit (pNF-H) is a major structural protein in axons. The pNF-H level is elevated in the serum of certain patients with central nervous disorders, including chemotherapy-induced cognitive impairment. The present study was conducted to elucidate the potential role of pNF-H as a marker of chemotherapy-induced peripheral neuropathy (CIPN). A total of 71 patients with early breast cancer in various stages of treatment (following 1, 3 or 7 cycles of chemotherapy, or a previous history of breast cancer chemotherapy) were assessed with a self-administered PainDETECT questionnaire [pain location, pain intensity on an 11-point numeric rating scale (NRS), and various pain qualities] and a single serum pNF-H measurement. Patients were divided into two groups based on the presence or absence of bilateral symmetric pain in the distal portions of the extremities [CIPN(+) or CIPN(-)]. The χ2 and Mann-Whitney tests were used for statistical analyses. Among the participants, only 8 patients complained of CIPN. Their pain intensity was 3.5±1.9 (mean ± standard deviation) compared with 1.5±1.8 in the CIPN(-) group (P<0.01). The NRS of numbness in the CIPN(+) group was significantly higher (2.4±1.4) than that of the CIPN(-) group (1.0±1.0). Increased pNF-H levels were observed in 37.5% of the CIPN(+) patients and in 23.8% of CIPN(-) patients (P=0.40). In conclusion, CIPN is observed in the most distal portions of the peripheral nerves that are composed of dendrites but not axons. Although serum pNF-H is a biomarker of axonal damage, it is not useful as a marker of CIPN.

[Importance of Anesthesiologists in the Work of a Palliative Care Team].

World Health Organization has proposed that palliative medicine should be applied early in the course of the malignant diseases. Regrettably, however, palliative care has been usually provided to patients with the advanced stage of cancer, as terminal care. Recently, palliative medicine begins at the time when patients are diagnosed with cancer. In response to changes in clinical settings of palliative medicine, anesthesiologists, with substantial experience in interdisciplinary pain management, can utilize their advantages in providing palliative medicine to cancer patients: 1) use of opioid analgesics; 2) considering the biopsychosocial model of pain; 3) helping patients live as actively as possible until death; and 4) helping the family cope with the patient's illness and their own bereavement.

[Understanding Opioid-induced Adverse Effects and its Managements].

Opioids are potent analgesics and improve both noci- ceptive and neuropathic pain. However, some patients suffer opioid-induced adverse effects, including not only somnolence, nausea and vomiting, and constipation (bowel dysfunction) but also osteoporosis, immunode- ficiency, paradoxical hyperalgesia and addiction. These adverse effects could derive from stimulating opioid receptors either in the central nervous system or at the periphery. Here, we explain the mechanisms of opioid-induced adverse effects and respective manage- ments of them. To control opioid-induced constipation, the peripheral-acting mu-opioid receptor antagonists (PAMORAs) have been widely used in USA. We dis- cuss features of and expectations for PAMORAs in Japan. Further, to avoid developing opioid addiction, we introduce the concept of 'Health literacy' and the measuring tool 'Newest Vital Sign Japanese version'. Controlling pain by opioids adequately and preventing and managing opioid-induced adverse effects ade- quately can result in improvement of QOL of patients with chronic pain.

Minocycline Does Not Decrease Intensity of Neuropathic Pain Intensity, But Does Improve Its Affective Dimension.

Recent understanding of the neuron-glia communication shed light on an important role of microglia to develop neuropathic pain The analgesic effect of minocycline on neuropathic pain is promising but it remains unclear in clinical settings. This study included 20 patients with neuropathic pain of varied etiologies. We administered 100 mg/day of minocycline for 1 week and then 200 mg/day for 3 weeks, as an open-label adjunct to conventional analgesics. An 11-point numerical rating scale. (NRS) and the short-form McGill Pain Questionnaire (SF-MPQ) were used to evaluate pain severity. The data were collected at baseline and after 4 weeks of therapy and analyzed using the Wilcoxon signed-rank test. All except two of the patients tolerated the full dose of minocycline. There was no significant improvement in the scoring of NRS (5.6 ± 1.2 at baseline vs. 5.3 ± 1.9 at 4 weeks; P =.60). The total score of the SF-MPQ decreased significantly (17.2 ± 7.4 vs. 13.9 ± 9.6; P =.02), particularly in the affective subscale (4.4 ± 2.7 vs. 3.3 ± 3.6; P =.007) but not so in the sensory subscale (12.8 ± 5.2 vs. 10.6 ± 6.2; P =.06). We conclude that minocycline failed to decrease pain intensity but succeeded in reducing the affective dimension associated with neuropathic pain.

[Neurorehabilitation for Neuropathic Pain].

Deafferentation, like as in limb amputation, brachial plexus avulsion injury and spinal cord injury, is usually followed by neuropathic pain. Neuropathic pain is a debilitating condition and it impairs the quality of life profoundly. Based on recent advances in the cognitive neuroscience, we explain intimate relationships among neuropathic pain, reorganization of primary sensory and motor cortices and the sensorimotor integration of the deafferentated limb. From the standpoint of the sensorimotor integration theory for emerging phantom limb pain, we further discuss the analgesic mechanism of neurorehabilitation techniques such as mirror visual feedback treatment and its related neurorobotics advancement for neuropathic pain.

Oral Local Anesthesia Successfully Ameliorated Neuropathic Pain in an Upper Limb Suggesting Pain Alleviation through Neural Plasticity within the Central Nervous System: A Case Report.

Neural blockades are considered an alternative to pharmacotherapy for neuropathic pain although these blockades elicit limited effects. We encountered a patient with postbrachial plexus avulsion injury pain, which was refractory to conventional treatments but disappeared temporarily with the administration of the local anesthetic lidocaine around the left mandibular molar tooth during dental treatments. This analgesic effect on neuropathic pain by oral local anesthesia was reproducible. Under conditions of neuropathic pain, cerebral somatotopic reorganization in the sensorimotor cortices of the brain has been observed. Either expansion or shrinkage of the somatotopic representation of a deafferentated body part correlates with the degree of neuropathic pain. In our case, administration of an oral local anesthetic shrank the somatotopic representation of the mouth, which is next to the upper limb representation and thereby expanded the upper limb representation in a normal manner. Consequently, oral local anesthesia improved the pain in the upper limb. This case suggests that pain alleviation through neural plasticity within the brain is related to neural blockade.