Pulsed Radiofrequency of Pudendal Nerve for Treatment in Patients with Pudendal Neuralgia. A Case Series with Long-Term Follow-Up.

Pudendal neuralgia (PN) is an impairing neuropathic disorder, affecting both men and women, involving a severe burning and sharp pain along the course of the pudendal nerve. Treatment is often insufficient, and options are limited. Pulsed radiofrequency (PRF) is a technique which might be useful in therapy. This case series aims to determine the effectiveness of PRF in patients with PN in the context of evaluation of care. Between 2010 and 2016, all female patients of University Medical Center Utrecht diagnosed with PN who experience insufficient pain relief after common treatment were offered PRF. Patient Global Impression of Improvement (PGI-I) scores were assessed at 3-month follow-up and at long-term follow-up (median 4 years). PGI-I scores were recorded to evaluate our quality of care. Twenty patients with PN consented to undergo PRF. We lost one patient in follow-up. Seventy-nine percent of the patients described their condition as "(very) much better" at 3-month follow-up. At long-term follow-up, 89% of the patients described their condition as "(very) much better." No serious side effects were observed. In conclusion, PRF is a successful treatment option in patients not responding to standard treatment options, including pudendal nerve blocks. PRF of the pudendal nerve can be used for PN to provide relief in patients' chronic pelvic pain.

Cost-effectiveness of vaccination of immunocompetent older adults against herpes zoster in the Netherlands: a comparison between the adjuvanted subunit and live-attenuated vaccines.

BACKGROUND: The newly registered adjuvanted herpes zoster subunit vaccine (HZ/su) has a higher efficacy than the available live-attenuated vaccine (ZVL). National decision-makers soon need to decide whether to introduce HZ/su or to prefer HZ/su above ZVL. METHODS: Using a Markov model with a decision tree, we conducted a cost-effectiveness analysis of vaccination with HZ/su (two doses within 2 months) or zoster vaccine live (ZVL) (single dose, or single dose with a booster after 10 years) for cohorts of 50-, 60-, 70- or 80-year-olds in the Netherlands. The model was parameterized using vaccine efficacy data from randomized clinical trials and up-to-date incidence, costs and health-related quality of life data from national datasets. We used a time horizon of 15 years, and the analysis was conducted from the societal perspective. RESULTS: At a coverage of 50%, vaccination with two doses of HZ/su was estimated to prevent 4335 to 10,896 HZ cases, depending on the cohort age. In comparison, this reduction was estimated at 400-4877 for ZVL and 427-6466 for ZVL with a booster. The maximum vaccine cost per series of HZ/su to remain cost-effective to a willingness-to-pay threshold of €20,000 per quality-adjusted life year (QALY) gained ranged from €109.09 for 70-year-olds to €63.68 for 50-year-olds. The cost-effectiveness of ZVL changed considerably by age, with corresponding maximum vaccine cost per dose ranging from €51.37 for 60-year-olds to €0.73 for 80-year-olds. Adding a ZVL booster after 10 years would require a substantial reduction of the maximum cost per dose to remain cost-effective as compared to ZVL single dose. Sensitivity analyses on the vaccine cost demonstrated that there were scenarios in which vaccination with either HZ/su (two doses), ZVL single dose or ZVL + booster could be the most cost-effective strategy. CONCLUSIONS: A strategy with two doses of HZ/su was superior in reducing the burden of HZ as compared to a single dose or single dose + booster of ZVL. Both vaccines could potentially be cost-effective to a conventional Dutch willingness-to-pay threshold for preventive interventions. However, whether HZ/su or ZVL would be the most cost-effective alternative depends largely on the vaccine cost.

EUS-guided celiac ganglia neurolysis: a clinical and human cadaver study (with video).

BACKGROUND AND AIMS: There is little evidence that structures targeted during EUS-guided celiac ganglia neurolysis (EUS-CGN) are celiac ganglia and that selective ethanol injection into ganglia is feasible. We aimed to visualize celiac ganglia, confirm that these structures are ganglia, and visualize ethanol spread after EUS-CGN and EUS-guided celiac plexus neurolysis (EUS-CPN). METHODS: First, celiac ganglia were sought during 97 consecutive EUS procedures. Second, ganglia were identified in a prosected human cadaver by placing a linear echoendoscope next to the celiac trunk and removing the underlying tissue for histology. Finally, various EUS-CGN and EUS-CPN techniques were performed in human cadavers; EUS-CGN was performed with 1 mL ethanol in 1 ganglion, 1 mL per ganglion (both low volume), and 4 mL per ganglion (high volume). EUS-CPN was performed with a central (20 mL) and a bilateral (2*10 mL) approach. Transverse sections (75 µm) were obtained and photographed to allow visualization of the spread of ethanol. RESULTS: A total of 204 ganglia were detected in 83 patients. Mean (± standard deviation) size of the long axis was 8.1 mm (± 7.4 mm). Histology of the removed region in the cadaver showed only nerve cell bodies. After low-volume EUS-CGN in cadavers, ethanol spread well beyond the targeted ganglion. After high-volume EUS-CGN in cadavers, a larger ethanol spread was seen, which also reached unidentified ganglia; the spread was comparable to the spread after EUS-CPN. CONCLUSIONS: Specific EUS-CGN is not feasible because ethanol spreads well beyond the targeted ganglion. Unidentified celiac ganglia are better reached with high-volume EUS-CGN, and this would likely result in a more thorough neurolysis. High-volume EUS-CGN should be preferred to low-volume EUS-CGN.

Pain, Itch, Quality of Life, and Costs after Herpes Zoster.

BACKGROUND: Herpes zoster (HZ) and postherpetic neuralgia are known to have a profound effect on the patient's quality of life, but the incidence and severity of itch and its relation with pain and quality of life in the long term are still relatively unknown. OBJECTIVE: The aim of this study was to measure the presence and severity of pain and itch and impact on quality of life in patients over 50 years old with HZ. METHODS: We enrolled 661 patients with HZ in this 12-month observational study. Patient data were collected via a web-based questionnaire. Outcomes were pain, itch, burden of illness, impact on patient's daily life, impact on quality of life, and healthcare costs. RESULTS: At inclusion, 94% of patients reported any pain, 74.3% significant pain, and 26% severe pain. After 3 months, 18.8% of patients suffered from postherpetic neuralgia. At inclusion, 70.8% of patients had any itch, 39.2% significant itch, and 7.3% severe itch. The occurrence of pain increases costs and has a high impact on the quality of life, lowering EQ-5D scores by an average of 18%. In contrast, itch has little effect on the quality of life. CONCLUSIONS: Pain and itch are highly prevalent months after HZ. Pain caused by HZ has a large impact on quality of life, burden of illness, impact on daily life, and health care costs for these patients. The impact of itch on quality of life is relatively small.

The effect of a preoperative educational film on patients' postoperative pain in relation to their request for opioids.

Guidelines for postoperative pain treatment are based on patients' pain scores. Patients with an intermediate Numeric Rating Scale (NRS) score of 5 or 6 may consider their pain as either bearable or unbearable, which makes it difficult to decide on pain treatment because guidelines advise professionals to treat pain at NRS > 4. Educating patients in using an NRS score for pain might improve adequate pain treatment. A quasi-randomized controlled trial was conducted in which 194 preoperative patients watched the educational film and 183 the control film. Pain scores were considered discordant when patients reported an NRS ≤ 4 and wanted additional opioids or when patients reported an NRS > 4 and did not want additional opioids. Beliefs, fear, and knowledge of pain; pain assessment; and pain treatment were measured by questionnaires. No significant differences in discordant pain scores between the groups were found: relative risk (RR) 0.73, confidence interval (CI) 0.47-1.15 at rest and RR 0.96, CI 0.72-1.28 at movement. Patients in the intervention group had lower NRS pain scores than patients in the control group. In the intervention group, patients had significantly more knowledge and lower barriers to pain management compared with the control group. We did not find a statistically significant reduction in discordant pain scores when comparing the intervention group with the control group. However, patients in the intervention group had significantly lower pain scores, lower barriers, and more knowledge of pain treatment than patients in the control group.

The Relation Between Patients' NRS Pain Scores and Their Desire for Additional Opioids after Surgery.

BACKGROUND: Postoperative pain is commonly assessed through a numerical rating scale (NRS), an 11-point scale where 0 indicates no pain and 10 indicates the worst imaginable pain. Guidelines advise the administration of analgesics at NRS pain scores above 3 or 4. In clinical practice, not all patients with pain scores above the treatment threshold are willing to accept additional analgesic treatment, especially when opioids are offered. The objective of this study is to measure the relation between patients' NRS pain scores and their desire for additional opioids. METHODS: This cross-sectional study examined 1,084 patients in an academic hospital the day after surgery between January 2010 and June 2010. The day after surgery, patients were asked to score their pain and desire for opioids. Sensitivity, specificity, positive predictive value, and negative predictive value of the desire for opioids and the different NRS thresholds were calculated. RESULTS: Only when patients scored an 8 or higher on the NRS did the majority express a need for opioids. Many patients did not desire opioids, because they considered their pain tolerable, even at an NRS score above 4. CONCLUSIONS: With the current guidelines (ie, using pain scores above 3 or 4 for prescribing opioids), many patients could be overtreated. Therefore, scores generated by the NRS should be interpreted individually.

Procedure-specific risk factor analysis for the development of severe postoperative pain.

BACKGROUND: Many studies have analyzed risk factors for the development of severe postoperative pain with contradictory results. To date, the association of risk factors with postoperative pain intensity among different surgical procedures has not been studied and compared. METHODS: The authors selected precisely defined surgical groups (at least 150 patients each) from prospectively collected perioperative data from 105 German hospitals (2004-2010). The association of age, sex, and preoperative chronic pain intensity with worst postoperative pain intensity was studied with multiple linear and logistic regression analyses. Pooled data of the selected surgeries were studied with random-effect analysis. RESULTS: Thirty surgical procedures with a total number of 22,963 patients were compared. In each surgical procedure, preoperative chronic pain intensity and younger age were associated with higher postoperative pain intensity. A linear decline of postoperative pain with age was found. Females reported more severe pain in 21 of 23 surgeries. Analysis of pooled surgical groups indicated that postoperative pain decreased by 0.28 points (95% CI, 0.26 to 0.31) on the numeric rating scale (0 to 10) per decade age increase and postoperative pain increased by 0.14 points (95% CI, 0.13 to 0.15) for each higher score on the preoperative chronic pain scale. Females reported 0.29 points (95% CI, 0.22 to 0.37) higher pain intensity. CONCLUSIONS: Independent of the type and extent of surgery, preoperative chronic pain and younger age were associated with higher postoperative pain. Females consistently reported slightly higher pain scores regardless of the type of surgery. The clinical significance of this small sex difference has to be analyzed in future studies.

The effects of glucocorticoids on neuropathic pain: a review with emphasis on intrathecal methylprednisolone acetate delivery.

Methylprednisolone acetate (MPA) has a long history of use in the treatment of sciatic pain and other neuropathic pain syndromes. In several of these syndromes, MPA is administered in the epidural space. On a limited basis, MPA has also been injected intrathecally in patients suffering from postherpetic neuralgia and complex regional pain syndrome. The reports on efficacy of intrathecal administration of MPA in neuropathic pain patients are contradictory, and safety is debated. In this review, we broadly consider mechanisms whereby glucocorticoids exert their action on spinal cascades relevant to the pain arising after nerve injury and inflammation. We then focus on the characteristics of the actions of MPA in pharmacokinetics, efficacy, and safety when administered in the intrathecal space.

Pain intensity on the first day after surgery: a prospective cohort study comparing 179 surgical procedures.

BACKGROUND: Severe pain after surgery remains a major problem, occurring in 20-40% of patients. Despite numerous published studies, the degree of pain following many types of surgery in everyday clinical practice is unknown. To improve postoperative pain therapy and develop procedure-specific, optimized pain-treatment protocols, types of surgery that may result in severe postoperative pain in everyday practice must first be identified. METHODS: This study considered 115,775 patients from 578 surgical wards in 105 German hospitals. A total of 70,764 patients met the inclusion criteria. On the first postoperative day, patients were asked to rate their worst pain intensity since surgery (numeric rating scale, 0-10). All surgical procedures were assigned to 529 well-defined groups. When a group contained fewer than 20 patients, the data were excluded from analysis. Finally, 50,523 patients from 179 surgical groups were compared. RESULTS: The 40 procedures with the highest pain scores (median numeric rating scale, 6-7) included 22 orthopedic/trauma procedures on the extremities. Patients reported high pain scores after many "minor" surgical procedures, including appendectomy, cholecystectomy, hemorrhoidectomy, and tonsillectomy, which ranked among the 25 procedures with highest pain intensities. A number of "major" abdominal surgeries resulted in comparatively low pain scores, often because of sufficient epidural analgesia. CONCLUSIONS: Several common minor- to medium-level surgical procedures, including some with laparoscopic approaches, resulted in unexpectedly high levels of postoperative pain. To reduce the number of patients suffering from severe pain, patients undergoing so-called minor surgery should be monitored more closely, and postsurgical pain treatment needs to comply with existing procedure-specific pain-treatment recommendations.

Reactivity in pain-free subjects and a clinical pain population: evaluation of the Kohn Reactivity Scale-dutch Version.

BACKGROUND: Patients with pain are more reactive to various types of sensations, not limited to pain alone. A potential useful instrument to assess reactivity is the Kohn Reactivity Scale (KRS). This study examines the psychometric characteristics of the KRS-Dutch version and its ability to differentiate between subjects with and without pain. METHODS: Internal consistency, convergent validity, and test-retest reliability of the Dutch translation of the KRS were assessed in 321 pain-free control subjects and different subgroups of this sample. Subsequently, reactivity scores were compared between the pain-free subjects and 291 pain patients who were referred to a pain clinic for treatment. RESULTS: Reliability analyses indicated good internal consistency (α ≥ 0.77) and high test-retest reliability (intraclass correlation = 0.95) of the KRS in the control subjects. Validity analyses yielded positive correlations of the KRS with related constructs like pain vigilance and awareness (r = 0.37), symptom severity (r = 0.29), and the personality characteristic neuroticism (r = 0.20). Pain patients had overall significantly higher KRS scores than the pain-free subjects indicating increased reactivity, particularly for the patients with medically unexplained pain. CONCLUSIONS: These findings indicate that the KRS is a useful instrument to screen for reactivity in pain patients, which may be of particular relevance for those suffering from medically unexplained pain.

Impact of physicians' sex on treatment choices for low back pain.

BACKGROUND: Little information is available regarding physicians' sex as a potential bias in making pain treatment decisions. This study investigated how sex of the medical care provider and patient characteristics influence choices that are made in the treatment of low back pain. METHODS: Data of 186 charts of patients with low back pain (46% males) who were seen by trained residents were analyzed in this retrospective observational study. The primary outcome was the first treatment choice that was made, which was categorized in three groups: pharmacological therapy; invasive procedures; or other options at the time of first consultation. Chi-square statistics and multinominal logistic regression analysis were used to examine associations between physicians' and/or patients' sex and treatment choices. RESULTS: Physicians' sex was found to be a significant predictor of the first decision that was made in the treatment of low back pain. Female physicians tended to prescribe more pharmacological agents as their first treatment choice. No significant sex differences were found for invasive therapies or other treatment options as a first choice. These findings were found to be independent from previous received pain therapies before consultation by the specialized pain clinician. Further, patients' sex did not influence decisions on pain management nor did gender concordance or discordance in the patient-physician relationship. CONCLUSIONS: Physicians' sex had a significant impact on pain management decisions in patients with low back pain. Female physicians prescribed more pharmacological agents as their first choice compared to male physicians.

Safety assessment and pharmacokinetics of intrathecal methylprednisolone acetate in dogs.

BACKGROUND: Intrathecal methylprednisolone acetate (MPA) has been used in patients with chronic pain syndromes. Its safety has been debated after reports of adverse events. No systematic preclinical evaluation of MPA has been reported. In the current study, the acute and long-term effects of intrathecal MPA on dog spinal tissue was studied with the injectate reformulated to include minimal adjuvants. METHODS: Seventeen dogs were implanted with intrathecal catheters and randomized to three groups: vehicle (lidocaine; 4 dogs), MPA 20 mg/ml (human dose; 7 dogs), and MPA 80 mg/ml (maximum deliverable dose; 6 dogs). In parallel with the human protocols, dogs received four injections at 7-day intervals. Clinical observations and plasma methylprednisolone measurements were done before and at intervals after intrathecal delivery. One week (acute) or 6 weeks (long-term) after the last injection, animals were sacrificed and spinal tissues harvested for histopathology. RESULTS: Other than a brief motor block, no adverse clinical event occurred in any animal. Group A (vehicle) showed minimal histologic changes (median histology-score; acute: 1.3, long-term: 1.0). Group B (MPA 20 mg/ml) had a diffuse inflammatory reaction (acute: 2.0, long-term: 3.0), group C (MPA 80 mg/ml) a severe inflammatory response, with large inflammatory masses (acute: 4.0, long-term: 7.0) The severity of the inflammatory reaction increased significantly with increasing dose at long-term sacrifice (acute P = 0.167, long-term P = 0.014). No neuronal injury, demyelination, or gliosis was seen in any animal. CONCLUSION: These results, showing dose-dependent intrathecal inflammatory reactions at MPA doses and injectate concentrations comparable to those used in humans, indicate that the continued use of this modality in humans is not recommended.

Executive and attentional functions in chronic pain: does performance decrease with increasing task load?

BACKGROUND: Diminished executive function and attentional control has been reported in chronic pain patients. However, the precise pattern of impairment in these aspects of cognition in chronic pain remains unclear. Moreover, a decline in psychomotor speed could potentially influence executive and attentional control performance in pain patients. OBJECTIVE: To examine different aspects of executive and attentional control in chronic pain together with the confounding role of psychomotor slowing. METHODS: Neuropsychological tests of sustained attention, planning ability, inhibition and mental flexibility were administered to 34 participants with chronic pain and 32 control participants. RESULTS: Compared with the controls, participants with chronic pain took longer to complete tests of sustained attention and mental flexibility, but did not perform worse on inhibition or planning tasks. The decreased performance on the mental flexibility task likely reflects a reduction in psychomotor speed. The pattern of performance on the sustained attention task reveals a specific decline in attention, indicated by a disproportionate decline in performance with an increase in task duration and by increased fluctuations in attention during task performance. No additional effect was noted of pain intensity, pain duration, pain catastrophizing, depressive symptoms, reduced sleep because of the pain or opioid use. CONCLUSIONS: Executive and attention functions are not uniformly affected in chronic pain. At least part of the previously reported decline in executive function in this group may reflect psychomotor slowing. Overall, limited evidence was found that executive and attention performance is indeed lower in chronic pain. Therefore, it can be concluded that in chronic pain sustained attention performance is diminished while mental flexibility, planning and inhibition appear to be intact.

The diagnostic value of the numeric pain rating scale in older postoperative patients.

AIMS AND OBJECTIVES: To measure the diagnostic value of the Numeric Rating Scale by comparing it to a Verbal Rating Scale in older patients. BACKGROUND: Pain management in older patients is an important challenge because of their greater susceptibility to adverse effects of analgesics. Nurses play an important role in applying guidelines for postoperative pain treatment. However, effective pain management is dependent upon valid and reliable pain assessment. DESIGN: Cross-sectional study. METHODS: In total, 2674 older patients scored their postoperative pain on an 11-point numeric rating scale (NRS) and an adjective scale (VRS) including no pain, little pain, painful but bearable, considerable pain and terrible pain. The diagnostic value of different NRS cut-off values for administering analgesics is determined by an ROC curve. RESULTS: Sensitivity of NRS > 3 for 'unbearable' pain in older patients was 72% with a specificity of 97·2%. With a cut-off point NRS > 4, sensitivity increased to 83%, while specificity was 96·7%. With a cut-off point NRS > 5, sensitivity was 94%, while specificity was 85%. A high proportion (75%) of older old patients (≥ 75 years) with 'painful but bearable' considers NRS 4, 5 and 6 to this VRS category. CONCLUSION: Using an NRS cut-off point > 3 or > 4, a large group of older patients with 'bearable' pain would incorrectly classified as 'unbearable'. When we make the assumption that bearable pain means no wish for additional analgesics, this misclassification might result in overtreatment with analgesics, while 3% would be undertreated. With NRS cut-off point > 5, 6% have a risk of overtreatment and 15% of undertreatment. RELEVANCE TO CLINICAL PRACTICE: Nurses should not rely solely on the NRS score in determining pain treatment; they need to communicate with older patients about their pain, the need for analgesics and eventual misconceptions about analgesics.

Relevance of physical fitness levels and exercise-related beliefs for self-reported and experimental pain in fibromyalgia: an explorative study.

BACKGROUND: It has been suggested that low physical fitness is a contributor to pain in fibromyalgia and that exercise-related beliefs play a role in the persistence of this association. Yet the association between physical fitness and pain is hardly explored in detail. OBJECTIVES: The aim of this exploratory study in patients with fibromyalgia was to investigate the association of physical fitness levels with self-reported and experimental pain as well as with pain catastrophizing and activity-avoidance beliefs. METHODS: Physical fitness of 18 patients with fibromyalgia was examined using maximal ergocycling and the 6-minute walking test (6MWT). Pain intensity was assessed using self-report scales and quantitative sensory testing. RESULTS: A reduced walking distance on the 6MWT was correlated with more severe self-reported pain on the Fibromyalgia Impact Questionnaire (r = -0.52, P < 0.05). Recovery of heart rate after ergocycling was correlated with cold pain thresholds (r = 0.70, P < 0.01), pressure pain thresholds (r = -0.70, P < 0.01), and heat wind-up (r = 0.66, P < 0.05). Activity-avoidance beliefs correlated with a lower peak VO2 on the cycle test (r = -0.52, P < 0.05), a shorter distance on the 6MWT (r = -0.56, P < 0.05), and more severe self-reported pain (r = 0.61, P < 0.05), reflecting that patients with activity-avoidance beliefs were less physically fit and experienced more severe pain. CONCLUSIONS: The results demonstrate some associations between physical fitness and pain in fibromyalgia and point to the importance of activity avoidance. Although the causal directionality of the associations needs substantiation in clinical research, the findings support the notion that low fitness and activity-avoidance beliefs should be targeted while treating pain in fibromyalgia.

Evidence-based interventional pain medicine according to clinical diagnoses. 17. Herpes zoster and post-herpetic neuralgia.

Herpes zoster infection is caused by a reactivation of the latent varicella zoster virus that causes chicken pox. It appears predominantly in older adults whose immunity for the virus has waned. The natural course of the disease is usually favorable, and the symptoms disappear spontaneously within a few weeks. Some patients, however, have prolonged pain: post-herpetic neuralgia. The diagnosis of acute zoster infection is made on the clinical signs including the appearance of rash. Post-herpetic neuralgia is described as sharp, burning, aching, or shooting constantly present in the dermatome that corresponds with the earlier rash. The objectives of treating herpes zoster are: (1) acute pain reduction; (2) promotion of recovery of epidermal defects and prevention of secondary infections; and (3) reduction or prevention of post-herpetic neuralgia. The objective of the treatment of post-herpetic neuralgia is primarily pain alleviation and improvement of the quality of life. Early treatment of the infection and the pain is believed to reduce the risk for post-herpetic neuralgia. This persistent pain syndrome is difficult to treat. Antiepileptic drugs and tricyclic antidepressants are the first choice. Interventional treatments, such as epidural injections of corticosteroids and local anesthetic drugs, have an effect on the acute pain but are of limited use in preventing post-herpetic neuralgia. When conservative treatment fails in providing satisfactory relief of post-herpetic neuralgia, a sympathetic block may be considered (2 C+); if this treatment provides unsatisfactory results, spinal cord stimulation may be considered, in a study context (2 C+).

Sensory Innervation of Human Bone: An Immunohistochemical Study to Further Understand Bone Pain.

Skeletal diseases and their surgical treatment induce severe pain. The innervation density of bone potentially explains the severe pain reported. Animal studies concluded that sensory myelinated A∂-fibers and unmyelinated C-fibers are mainly responsible for conducting bone pain, and that the innervation density of these nerve fibers was highest in periosteum. However, literature regarding sensory innervation of human bone is scarce. This observational study aimed to quantify sensory nerve fiber density in periosteum, cortical bone, and bone marrow of axial and appendicular human bones using immunohistochemistry and confocal microscopy. Multivariate Poisson regression analysis demonstrated that the total number of sensory and sympathetic nerve fibers was highest in periosteum, followed by bone marrow, and cortical bone for all bones studied. Bone from thoracic vertebral bodies contained most sensory nerve fibers, followed by the upper extremity, lower extremity, and parietal neurocranium. The number of nerve fibers declined with age and did not differ between male and female specimens. Sensory nerve fibers were organized as a branched network throughout the periosteum. The current results provide an explanation for the severe pain accompanying skeletal disease, fracture, or surgery. Further, the results could provide more insight into mechanisms that generate and maintain skeletal pain and might aid in developing new treatment strategies. PERSPECTIVE: This article presents the innervation of human bone and assesses the effect of age, gender, bone compartment and type of bone on innervation density. The presented data provide an explanation for the severity of bone pain arising from skeletal diseases and their surgical treatment.

Pain in patients with chronic idiopathic axonal polyneuropathy.

BACKGROUND/AIMS: Pain in patients with chronic idiopathic axonal polyneuropathy (CIAP) has never been studied in detail. The aim of the study was to investigate the pain experienced by patients with CIAP, and to determine whether pain is associated with health-related quality of life (HRQoL). METHODS: The McGill Pain Questionnaire (MPQ) and the RAND-36 were used in a cross-sectional study. RESULTS: Sixty-three of 91 patients with CIAP reported experiencing pain, describing it as nagging (56%) and annoying (52%). Of these patients, 27 were classified in a subgroup with neuropathic pain (median VAS = 33 mm), 25 in a subgroup with non-neuropathic pain (median VAS = 34 mm), and 11 in a mixed-pain subgroup (median VAS = 25 mm). Non-neuropathic pain was as common and as painful as neuropathic pain. Pain was strongly associated with the physical functioning domain of the RAND-36 in patients in the mixed pain subgroup (r = -0.71, p < 0.05). CONCLUSION: Neuropathic and non-neuropathic pain syndromes should be distinguished in patients with CIAP who experience pain, to enable appropriate tailoring of treatment.

An understanding of bone pain: A narrative review.

Skeletal pathologies are often accompanied by bone pain, which has negative effects on the quality of life and functional status of patients. Bone pain can be caused by a wide variety of injuries and diseases including (poorly healed) fractures, bone cancer, osteoarthritis and also iatrogenic by skeletal interventions. Orthopedic interventions are considered to be the most painful surgical procedures overall. Two major groups of medication currently used to attenuate bone pain are NSAIDs and opioids. However, these systemic drugs frequently introduce adverse events, emphasizing the need for alternative therapies that are directed at the pathophysiological mechanisms underlying bone pain. The periosteum, cortical bone and bone marrow are mainly innervated by sensory A-delta fibers and C-fibers. These fibers are mostly present in the periosteum rendering this structure most sensitive to nociceptive stimuli. A-delta fibers and C-fibers can be activated upon mechanical distortion, acidic environment and increased intramedullary pressure. After activation, these fibers can be sensitized by inflammatory mediators, phosphorylation of acid-sensing ion channels and cytokine receptors, or by upregulation of transcription factors. This can result in a change of pain perception such that normally non-noxious stimuli are now perceived as noxious. Pathological conditions in the bone can produce neurotrophic factors that bind to receptors on A-delta fibers and C-fibers. These fibers then start to sprout and increase the innervation density of the bone, making it more sensitive to nociceptive stimuli. In addition, repetitive painful stimuli cause neurochemical and electrophysiological alterations in afferent sensory neurons in the spinal cord, which leads to central sensitization, and can contribute to chronic bone pain. Understanding the pathophysiological mechanisms underlying bone pain in different skeletal injuries and diseases is important for the development of alternative, targeted pain treatments. These pain mechanism-based alternatives have the potential to improve the quality of life of patients suffering from bone pain without introducing undesirable systemic effects.

Recommendations for the management of herpes zoster.

The objective of this article is to provide evidence-based recommendations for the management of patients with herpes zoster (HZ) that take into account clinical efficacy, adverse effects, impact on quality of life, and costs of treatment. Systematic literature reviews, published randomized clinical trials, existing guidelines, and the authors' clinical and research experience relevant to the management of patients with HZ were reviewed at a consensus meeting. The results of controlled trials and the clinical experience of the authors support the use of acyclovir, brivudin (where available), famciclovir, and valacyclovir as first-line antiviral therapy for the treatment of patients with HZ. Specific recommendations for the use of these medications are provided. In addition, suggestions are made for treatments that, when used in combination with antiviral therapy, may further reduce pain and other complications of HZ.