Neuropathic Conditions Research Articles

Peripheral and Autonomic Neuropathy Status of Young Patients With Type 1 Diabetes Mellitus at the Time of Transition From Pediatric Care to Adult-Oriented Diabetes Care

IntroductionThe prevalence of neuropathic lesions in young patients with type 1 diabetes mellitus (T1DM) at the time of transition from pediatric care to adult-oriented diabetes care is poorly studied. A comparative study with healthy volunteers to assess the possible neuropathic condition of this special population and to identify the potential early screening needs has not been performed yet. The results may provide important feedback to pediatric diabetes care and a remarkable baseline reference point for further follow up in adult diabetes care.Patients and MethodsTwenty-nine young patients with T1DM [age: 22.4 ± 2.9 years; HbA1c: 8.5 ± 2.1%, diabetes duration: 12.2 ± 5.8 years; (mean ± SD)] and 30 healthy volunteers (age: 21.5 ± 1.6 years; HbA1c: 5.3 ± 0.3%) were involved in the study. Autonomic function was assessed by standard cardiovascular reflex tests. Complex peripheral neuropathic testing was performed by Neurometer®, Neuropad®-test, Tiptherm®, Monofilament®, and Rydel-Seiffer tuning fork tests.ResultsT1DM patients had significantly higher diastolic blood pressure than controls (80 ± 9 vs. 74 ± 8 mmHg, p < 0.01), but there was no significant difference in systolic blood pressure (127 ± 26 vs. 121 ± 13 mmHg). Cardiovascular reflex tests had not revealed any significant differences between the T1DM patients and controls. No significant differences with Neurometer®, Neuropad®-test, and Monofilament® were detected between the two groups. The vibrational sensing on the radius on both sides was significantly impaired in the T1DM group compared to the controls with Rydel-Seiffer tuning fork test (right: 7.5 ± 1.0 vs. 7.9 ± 0.3; left: 7.5 ± 0.9 vs. 7.9 ± 0.3, p < 0.05). The Tiptherm®-test also identified a significant impairment in T1DM patients (11 sensing failures vs. 1, p < 0.001). In addition, the neuropathic complaints were significantly more frequently present in the T1DM patient group than in the controls (9 vs. 0, p < 0.01).ConclusionIn this young T1DM population, cardiovascular autonomic neuropathy and cardiac morphological alterations could not be found. However, Rydel-Seiffer tuning fork and Tiptherm®-tests revealed peripheral sensory neurological impairments in young T1DM patients at the time of their transition to adult diabetes care.

Modality-Specific Modulation of Temperature Representations in the Spinal Cord after Injury.

Different types of tissue injury, such as inflammatory and neuropathic conditions, cause modality-specific alternations on temperature perception. There are profound changes in peripheral sensory neurons after injury, but how patterned neuronal activities in the CNS encode injury-induced sensitization to temperature stimuli is largely unknown. Using in vivo calcium imaging and mouse genetics, we show that formalin- and prostaglandin E2-induced inflammation dramatically increase spinal responses to heating and decrease responses to cooling in male and female mice. The reduction of cold response is largely eliminated on ablation of TRPV1-expressing primary sensory neurons, indicating a crossover inhibition of cold response from the hyperactive heat inputs in the spinal cord. Interestingly, chemotherapy medication oxaliplatin can rapidly increase spinal responses to cooling and suppress responses to heating. Together, our results suggest a push-pull mechanism in processing cold and heat inputs and reveal a synergic mechanism to shift thermosensation after injury.SIGNIFICANCE STATEMENT In this paper, we combine our novel in vivo spinal cord two-photon calcium imaging, mouse genetics, and persistent pain models to study how tissue injury alters the sensation of temperature. We discover modality-specific changes of spinal temperature responses in different models of injury. Chemotherapy medication oxaliplatin leads to cold hypersensitivity and heat hyposensitivity. By contrast, inflammation increases heat sensitivity and decreases cold sensitivity. This decrease in cold sensitivity results from the stronger crossover inhibition from the hyperactive heat inputs. Our work reveals the bidirectional change of thermosensitivity by injury and suggests that the crossover inhibitory circuit underlies the shifted thermosensation, providing a mechanism to the biased perception toward a unique thermal modality that was observed clinically in chronic pain patients.

Brainstem Pain-Modulation Circuitry and Its Plasticity in Neuropathic Pain: Insights From Human Brain Imaging Investigations.

Acute pain serves as a protective mechanism that alerts us to potential tissue damage and drives a behavioural response that removes us from danger. The neural circuitry critical for mounting this behavioural response is situated within the brainstem and is also crucial for producing analgesic and hyperalgesic responses. In particular, the periaqueductal grey, rostral ventromedial medulla, locus coeruleus and subnucleus reticularis dorsalis are important structures that directly or indirectly modulate nociceptive transmission at the primary nociceptive synapse. Substantial evidence from experimental animal studies suggests that plasticity within this system contributes to the initiation and/or maintenance of chronic neuropathic pain, and may even predispose individuals to developing chronic pain. Indeed, overwhelming evidence indicates that plasticity within this circuitry favours pro-nociception at the primary synapse in neuropathic pain conditions, a process that ultimately contributes to a hyperalgesic state. Although experimental animal investigations have been crucial in our understanding of the anatomy and function of the brainstem pain-modulation circuitry, it is vital to understand this system in acute and chronic pain states in humans so that more effective treatments can be developed. Recent functional MRI studies have identified a key role of this system during various analgesic and hyperalgesic responses including placebo analgesia, offset analgesia, attentional analgesia, conditioned pain modulation, central sensitisation and temporal summation. Moreover, recent MRI investigations have begun to explore brainstem pain-modulation circuitry plasticity in chronic neuropathic pain conditions and have identified altered grey matter volumes and functioning throughout the circuitry. Considering the findings from animal investigations, it is likely that these changes reflect a shift towards pro-nociception that ultimately contributes to the maintenance of neuropathic pain. The purpose of this review is to provide an overview of the human brain imaging investigations that have improved our understanding of the pain-modulation system in acute pain states and in neuropathic conditions. Our interpretation of the findings from these studies is often guided by the existing body of experimental animal literature, in addition to evidence from psychophysical investigations. Overall, understanding the plasticity of this system in human neuropathic pain conditions alongside the existing experimental animal literature will ultimately improve treatment options.

The Role of Glia Underlying Acupuncture Analgesia in Animal Pain Models, a Systematic Review and Meta-Analysis

Background: Acupuncture is proposed worldwide as a treatment for pain and other health problems, but the findings of acupuncture analgesia have been inconsistent. This study aims to evaluate the existing animal studies for evidence of acupuncture analgesia and its association of glia. Methods: Literature searches were performed in Web of Science, PubMed, EMBASE and CNKI through August 21st 2020. Preclinical studies of pain models with both pain and glial outcomes were included. Findings: A total of 43 studies in rodents were included. The analgesic effect of single-treatment was more effective in inflammatory pain (thermal: 4.02 (95%CI: 1.31~6.73); mechanical: 2.17 (95%CI: 0.97~3.38)) than neuropathic pain (thermal: 1.40 (95%CI: 0.85~1.94); mechanical: 1.93 (95%CI: 0.89~2.98)). Repeated-treatment was more curative in alleviating thermal pain in neuropathic condition (2.03, 95%CI: 1.60~2.46). Furthermore, acupuncture effectively inhibited the activation of astrocyte (inflammatory pain: -1.86 (95%CI: -2.73~-0.99), neuropathic pain: -2.39 (95%CI: -3.26~-1.52)) and microglia (inflammatory pain: -2.24 (95%CI: -2.91~-1.58), neuropathic pain: -1.92 (95%CI: -2.44~-1.41)) in a time-course pattern. Interpretation: Acupuncture improves analgesic effect under the possible mechanism of glia inhibition. These results provide an opportunity to evaluate the effectiveness of acupuncture analgesia in animal models to research further neurobiological mechanisms and to inform the design of future clinical trials. Funding: National Key R&D Program of China, the National Natural Science Foundation of China, Development Project of Shanghai Peak Disciplines Integrated Chinese and Western Medicine, Shanghai Science and Technology Committee Rising-Star Program, 111 Project, key project of Shanghai Science &Technology, Shanghai Municipal Science and Technology Major Project and ZJLab. Declaration of Interest: No conflicts of interest were disclosed.

Common and discrete mechanisms underlying chronic pain and itch: peripheral and central sensitization.

Normally, an obvious antagonism exists between pain and itch. In normal conditions, painful stimuli suppress itch sensation, whereas pain killers often generate itch. Although pain and itch are mediated by separate pathways under normal conditions, most chemicals are not highly specific to one sensation in chronic pathologic conditions. Notably, in patients with neuropathic pain, histamine primarily induces pain rather than itch, while in patients with atopic dermatitis, bradykinin triggers itch rather than pain. Accordingly, repetitive scratching even enhances itch sensation in chronic itch conditions. Physicians often prescribe pain relievers to patients with chronic itch, suggesting common mechanisms underlying chronic pain and itch, especially peripheral and central sensitization. Rather than separating itch and pain, studies should investigate chronic itch and pain including neuropathic and inflammatory conditions. Here, we reviewed chronic sensitization leading to chronic pain and itch at both peripheral and central levels. Studies investigating the connection between pain and itch facilitate the development of new therapeutics against both chronic dysesthesias based on the underlying pathophysiology.

Diagnostic accuracy of upper limb neurodynamic tests in the diagnosis of cervical radiculopathy

BackgroundUpper limb neurodynamic tests (ULNT) are used to diagnose neuropathic conditions such as cervical radiculopathy (CR). Within the literature, a positive ULNT is defined in markedly variable ways, which is likely why the diagnostic accuracy of these tests lacks consistency across studies. ObjectivesTo determine the diagnostic accuracy of single and combined upper limb neurodynamic tests ((ULNT)1,2a, 2b and 3) for cervical radiculopathy using test findings that are similar to those used in practice. DesignDiagnostic accuracy study (prospective) design following the updated STARD 2015 reporting guideline. MethodFrom 109 consecutively enrolled individuals with suspected CR. Of the 85 participants included, 27 (31.7%) were diagnosed with CR (mean age, 43.9years; Neck Disability Index 38,16%). ULNTs test were performed by a blind examiner to a CR reference standard of clinical diagnosis and magnetic resonance imaging verification provided by a neurosurgeon. ResultsIn general, the single tests were better at ruling in CR versus ruling out. Of the single ULNT, the ULNT3 demonstrated the strongest post-test probability change with a positive finding (73.28%). Three of four test combinations demonstrated the highest clinical utility for changing the post-test probability with a positive finding at 83.29% and with LR+ = 12.89 (95%CI: 3.10–53.62). Having none of the test's positive was able to rule out CR with LR- = 0.08 (95%CI: 0.01–0.56). ConclusionULNTs fail to significantly alter post-test probability when used singularly for diagnosis of CR. However, combinations of ULNT (3 out of 4 positive) can rule in CR, and rule out CR when all ULNT are negative.

In-Silico Validation and Fabrication of Matrix Diffusion-Based Polymeric Transdermal Patches for Repurposing Gabapentin Hydrochloride in Neuropathic Pain.

Gabapentin (GBP) is an FDA-approved drug for the treatment of partial and secondary generalized seizures, apart from being used for diabetic neuropathic pain. GBP displays a highly intricate mechanism of action and its inhibitory response in elevated antagonism of NMDA (N-methyl-D-aspartate receptor) receptor and thus, can be repurposed for controlling neuropathic pain. Therefore, in the present study, we have selected hBCATc (humanPyridoxal 5'-phosphate- dependent branched-chain aminotransferase cytosolic) gene that is highly expressed in silico validation through neuropathic stressed conditions. Thereafter, have analysed the GBP as its competitive inhibitor by in silico validation through homology modelling, molecular docking, also predicting its structural alerts and pharmacokinetic suitability through ADMET. However, and GBP was found to be a potential drug in controlling neuropathic pain, still, it has certain critical and pharmacokinetic limitations; therefore, the need for its targeted delivery was required, and the same was attained by designing a GBP loaded transdermal patch (GBP-TDP). A suitable and equally efficacious GBP - TDP was developed by a solvent evaporation method using PVP and HPMC in the ratio of 2:1 as a polymer base for reservoir type of TDP. Also, PEG 400 was used as a plasticizer, and PVA (4%) was taken for backing membrane preparation, and then the optimized GBP-TDP was subjected for physical characterization, optimization and ex vivo release kinetics. The results showed desired specifications with uneven and flaky surface appearance giving an avenue for controlled release of the drugs with 92.34 ± 1.43% of drug release in 10 hours, further suggesting that GBP-TDP can be used as an effective tool against diabetic neuropathy pain. In this study, we have repurposed Gabapentin to treat diabetic neuropathy and validated the same by conducting a detailed in silico evaluation starting from homology Modelling of the target protein hBCATc, cross verified by the Ramachandran plot analysis with the most favoured region of 92.1% (encompassing 303 residues out of 386).

Cytomegalovirus infection in Guillain-Barré syndrome: a retrospective study in Brazil.

Guillain-Barré syndrome (GBS) is currently the most common cause of acute flaccid paralysis worldwide. Risk factors for GBS include previous viral or bacterial infections or vaccination. Recently, an outbreak of Zika virus led to an outbreak of GBS in Latin America, mostly in Brazil, concomitant to continuous circulation of dengue virus serotypes. However, there is no study about cytomegalovirus (CMV) infection as a risk for GBS in Brazil. In this study, we report a series of cases of GBS with the aim of determining the prevalence of CMV and the characteristics associated with the infection. A cohort of 111 GBS cases diagnosed between 2011 and 2017 in Natal, northeastern Brazil, was studied. Presence of CMV IgM antibodies was determined by means of electrochemiluminescence. The analysis was performed considering CMV infection status and the clinical outcome. We found seroprevalence of 15.3% (n = 17) for CMV. CMV patients were younger (26 vs. 40; p = 0.016), with no apparent gastrointestinal (p = 0.762) or upper respiratory infections (p = 0.779) or sensory loss (p = 0.03). They presented more often with a classic GBS sensorimotor variant (p = 0.02) and with a demyelinating pattern in electrophysiological studies (p < 0.001). In Brazil, the clinical-epidemiological profile of GBS associated with CMV infection is similar to that described in other countries. Better understanding of the relationship between infectious processes and GBS is a key component of the research agenda and assistance strategy for global health initiatives relating to peripheral neuropathic conditions.

Treatment of Painful Diabetic Neuropathy-A Narrative Review of Pharmacological and Interventional Approaches.

Painful diabetic neuropathy (PDN) is a common complication of diabetes mellitus that is associated with a significant decline in quality of life. Like other painful neuropathic conditions, PDN is difficult to manage clinically, and a variety of pharmacological and non-pharmacological options are available for this condition. Recommended pharmacotherapies include anticonvulsive agents, antidepressant drugs, and topical capsaicin; and tapentadol, which combines opioid agonism and norepinephrine reuptake inhibition, has also recently been approved for use. Additionally, several neuromodulation therapies have been successfully used for pain relief in PDN, including intrathecal therapy, transcutaneous electrical nerve stimulation (TENS), and spinal cord stimulation (SCS). Recently, 10 kHz SCS has been shown to provide clinically meaningful pain relief for patients refractory to conventional medical management, with a subset of patients demonstrating improvement in neurological function. This literature review is intended to discuss the dosage and prospective data associated with pain management therapies for PDN.

Mechanistic Rationale and Clinical Efficacy of Hyperbaric Oxygen Therapy in Chronic Neuropathic Pain: An Evidence-Based Narrative Review.

Background Chronic neuropathic pain is a condition affecting an increasing proportion of the general population and its management requires a comprehensive, multidisciplinary program. A growing body of evidence supports the use of hyperbaric oxygen therapy (HBOT) in several chronic neuropathic pain conditions; however, its role and efficacy remain unclear. Purpose To summarize current evidence for the mechanistic rationale of HBOT in chronic neuropathic pain conditions and to evaluate its clinical efficacy. Methods This narrative review was conducted after searching the following databases (Medline, Embase, Cochrane, PsycINFO, the Web of Science, Scopus, ClinicalTrials. gov, WHO ICTRP, and ProQuest Digital Dissertation) from January 1946 to March 2020. Articles published in English that involved either animal or human studies with acute or chronic neuropathic pain evaluating any HBOT-related intervention were included. Results A total of 2971 citations were identified. A total of 29 studies were included in this review. The mechanisms of action for HBOT use in neuropathic conditions included the primary effects of hyperoxia and edema resolution, as well as the secondary effects pertinent to the production of oxygen and nitrogen reactive species (serving as pain signaling molecules), nitric oxide-dependent release of opioid peptides, and reduction of inflammatory mediators. A robust evidence for HBOT use in the clinical setting was associated with chronic regional pain syndrome and chronic primary bladder pain syndrome. Some evidence supported its use for chronic secondary (peripheral) neuropathic pain including radiation-induced plexus neuropathies, postherpetic neuralgia, and trigeminal neuralgia. Conclusions HBOT has been shown to have antinociceptive and analgesic effects in animal models of inflammatory, neuropathic, and chronic pain. Human studies demonstrated beneficial effects of HBOT in improving clinical outcomes such as pain scores, pain-related symptoms, and quality of life. A systematic methodology of HBOT application is necessary to confirm its safety and efficacy.

Drug Reaction with Eosinophilia and Systemic Symptoms and Agranulocytosis Presenting as Cervical Lymphadenopathy.

Objective: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare cause of cervical lymphadenopathy. It is a potentially life-threatening hypersensitivity reaction, commonly characterized by fever, rash, hematological abnormalities, and multi-organ involvement. Its association with agranulocytosis is even rarer, with fewer than 10 cases describing the coexistence of DRESS with agranulocytosis reported in the English literature. Case Summary: An otherwise well 40-year-old female presented with a sore throat and cervical lymphadenopathy, with investigations revealing DRESS and agranulocytosis secondary to carbamazepine. Conclusion: DRESS and agranulocytosis are serious, potentially life-threatening adverse drug reactions which can initially present as cervical lymphadenopathy. As carbamazepine is considered first-line therapy for certain chronic neuropathic conditions such as trigeminal neuralgia, clinicians should be aware of the varying clinical presentations of both conditions.

Clinical Outcome of Percutaneous Trigeminal Nerve Block in Elderly Patients in Outpatient Clinics.

ObjectiveTrigeminal neuralgia (TN) is a severe neuropathic condition that affects several elderly patients. It is characterized by uncontrolled pain that significantly impacts the quality of life of patients. Therefore, the condition should be treated as an emergency. In the majority of patients, pain can be controlled with medication; however, other treatment modalities are being explored in those who become refractory to drug treatment. The use of the trigeminal nerve block with a local anesthetic serves as an excellent adjunct to drug treatment. This technique rapidly relieves the patient of pain while medications are being titrated to effective levels. We report the efficacy and safety of percutaneous trigeminal nerve block in elderly patients with TN at our outpatient clinic. MethodsTwenty-one patients older than 65 years with TN received percutaneous nerve block at our outpatient clinic. We used bupivacaine (1 mL/injection site) to block the supraorbital, infraorbital, superior alveolar, mental, and inferior alveolar nerves according to pain sites of patients. ResultsAll patients reported relief from pain, which decreased by approximately 78% after 2 weeks of nerve block. The effect lasted for more than 4 weeks in 12 patients and for 6 weeks in two patients. There were no complications. ConclusionPercutaneous nerve block procedure performed at our outpatient clinic provided immediate relief from pain to elderly patients with TN. The procedure is simple, has no serious side effects, and is easy to apply.

A step closer in the management of uncontrolled neuropathic pain: gabapentin-nortriptyline combination

&lt;p class="abstract"&gt;Neuropathic pain is extremely distressing as it significantly hampers the performance of daily activities and impedes overall quality of life. A large number of illnesses are linked with neuropathic pain like radiculopathy, sciatica, diabetes, herpes infection, spinal injury, stroke, etc. Treating neuropathic pain is challenging as response to the treatment is at times uncertain and associated with undesirable side effects. Uncontrolled neuropathic pain is observed in large group of patients receiving current treatment regimen. Almost half of the neuropathic pain patients need more than two drugs for pain relief. Various clinical trials have demonstrated better efficacy of combination therapy in reducing pain than monotherapy. Utilizing drug combination with different mechanism of action or acting on two different sites has demonstrated superior analgesic effect in painful neuropathic condition. The first tier agents recommended by various guidelines are calcium channel alpha-2-delta ligands and tricyclic antidepressants that act on different pain pathways. A clinical trial has shown enhanced pain relief with no increase in side effects with the administration of gabapentin and nortriptyline combination in patients suffering from neuropathic pain. Moreover, symptoms associated with neuropathic pain like sleep disturbances, altered mood, decreased walking ability, depression and quality of life were also significantly improved. Hence, combination therapy of gabapentin and nortriptyline offers a pivotal modality in the management of uncontrolled neuropathic pain.&lt;/p&gt;

William F. Hoyt's Role in Identifying the Pathogenesis of Duane Retraction Syndrome.

For many years, it was unclear whether Duane retraction syndrome was a myopathic or neuropathic condition. This article describes the direct and indirect contributions of William F. Hoyt, MD, to the eventual determination that the condition is caused by a congenital absence of the sixth nerve combined with innervation of the lateral rectus muscle by branches of the third nerve.

Comparison of Gabapentin Monotherapy vs. Combination Therapy of Methyl Cobalamin and Gabapentin in Treating Diabetic Neuropathic Pain

Introduction: To evaluate effectiveness of gabapentin alone and combination therapy of gabapentin with methyl cobalamin with regards to decrease in pain in patients suffering from diabetic neuropathy. Method: Patients studied constituted either gender with age ranging above 18 year up to 80 years. Patients suffering from diabetic neuropathy were followed in this study. They had painful neuropathic condition and were following treatment for controlling diabetes mellitus. They were divided into two groups (1 and 2) according to the type of drug used for the purpose of neuropathic pain. Group 1 patients received Gabapentin monotherapy while Group 2 patients received combined therapy of gabapentin and Methylcobalamin. Variables such as age, gender, weight, BMI, type of drug used and pain score were noted in proformas and data was then analysed with SPSS (VERSION 16). Results: There were two groups of patients. One hundred fifty patients were receiving gabapentin (group 1). While other 150 subjects were put on the combination regimen of Gabapentin and Methyl cobalamine (group 2). On comparison of scores for pain between the two groups there was significant difference of pain decrease in the combination therapy group 2 as compared to the solo drug usage (gabapentin) in group 1. No adverse side effects of much significance were noted. Conclusion: It is inferred from this study that combined therapy with Gabapentin and Methylcobalamin can be more efficacious as compared to treatment with gabapentin alone. This combination is safe with minimal side effects.

No pain, still gain (of function): the relation between sensory profiles and the presence or absence of self-reported pain in a large multicenter cohort of patients with neuropathy.

The pathophysiology of pain in neuropathy is complex and may be linked to sensory phenotypes. Quantitative sensory testing, a standardized method to evaluate sensory profiles in response to defined stimuli, assesses functional integrity of small and large nerve fiber afferents and central somatosensory pathways. It has revealed detailed insights into mechanisms of neuropathy, yet it remains unclear if pain directly affects sensory profiles. The main objective of this study was to investigate sensory profiles in patients with various neuropathic conditions, including polyneuropathy, mononeuropathy, and lesions to the central nervous system, in relation to self-reported presence or absence of pain and pain sensitivity using the Pain Sensitivity Questionnaire. A total of 443 patients (332 painful and 111 painless) and 112 healthy participants were investigated. Overall, loss of sensation was equally prevalent in patients with and without spontaneous pain. Pain thresholds were equally lowered in both patient groups, demonstrating that hyperalgesia and allodynia are just as present in patients not reporting any pain. Remarkably, this was similar for dynamic mechanical allodynia. Hypoalgesia was more pronounced in painful polyneuropathy, whereas hyperalgesia was more frequent in painful mononeuropathy (compared with painless conditions). Self-reported pain sensitivity was significantly higher in painful than in painless neuropathic conditions. Our results reveal the presence of hyperalgesia and allodynia in patients with central and peripheral lesions of the somatosensory system not reporting spontaneous pain. This shows that symptoms and signs of hypersensitivity may not necessarily coincide and that painful and painless neuropathic conditions may mechanistically blend into one another.

Clinical Significance and Diagnostic Value of Pain Extent Extracted from Pain Drawings: A Scoping Review.

The current scoping review aimed to map current literature investigating the relationship between pain extent extracted from pain drawings with clinical, psychological, and psycho-physiological patient-reported outcome measures in people with pain. Electronic databases were searched for cross-sectional cohort studies that collected pain drawings using digital technology or a pen-on-paper approach and assessed for correlations between pain extent and clinical, psychological or psycho-physical outcomes. Data were extracted by two different reviewers. The methodological quality of studies was assessed using the Newcastle–Ottawa Quality Assessment Scale. Mapping of the results included: 1, description of included studies; 2, summary of results; and 3, identification of gaps in the existing literature. Eleven cross-sectional cohort studies were included. The pain disorders considered were heterogeneous, ranging from musculoskeletal to neuropathic conditions, and from localized to generalized pain conditions. All studies included pain and/or pain-related disability as clinical outcomes. Psychological outcomes included depression and anxiety, kinesiophobia and catastrophism. Psycho-physical measures included pressure or thermal pain thresholds. Ten studies were considered of high methodological quality. There was heterogeneity in the associations between pain extent and patient-reported outcome measures depending on the pain condition. This scoping review found that pain extent is associated with patient-reported outcome measures more so in patients presenting with musculoskeletal pain, e.g., neck pain or osteoarthritis, rather than for those with neuropathic pain or headache.

Peripheral Deltorphin II Inhibits Nociceptors Following Nerve Injury.

Clinical and preclinical studies have revealed that local administration of opioid agonists into peripheral tissue attenuates inflammatory pain. However, few studies have examined whether peripherally restricted opioids are effective in reducing mechanical allodynia and hyperalgesia that usually follows nerve injury. The aim of the present study was to determine whether the mechanical responsiveness of C-fiber mechanical nociceptors innervating skin under neuropathic pain conditions is depressed by direct activation of delta opioid receptors (DORs) on their peripheral terminals. A murine model of peripheral neuropathic pain was induced with a spared nerve (tibial) injury, in which mice survived 7 or 28 days after surgery before electrophysiological testing began. Control groups comprised naïve and sham-operated animals. An ex vivo preparation of mouse plantar skin with attached tibial nerve was used to examine electrophysiologically the effects of the selective DOR agonist, deltorphin II, on the response properties of individual cutaneous C-fiber nociceptors. In contrast to naïve and sham-operated animals, deltorphin II induced an inhibition of the mechanical responsiveness of C-fiber mechanical nociceptors innervating skin under neuropathic conditions. The effects of deltorphin II were concentration-dependent and prevented by pretreatment with naltrindole indicating DOR-mediated inhibitory effects of deltorphin II. Our results provide the first direct evidence for expression of functional DORs on mechanical nociceptors innervating skin in an animal model of neuropathic pain.

Treatment of “plantar fasciitis”/Plantar Heel Pain Syndrome with botulinum toxin — A novel injection paradigm pilot study

Randomized controlled trials over the last two decades, although promising with favorable results, have shown varied efficacy in treatment of “plantar fasciitis” with botulinum toxin injection11Clinicaltrials.gov, NIH, National Libraries of Medicine.. One reason may be due to conflating the variabilities of plantar heel conditions solely as plantar fasciitis. Plantar Heel Pain Syndrome can be of one or more etiologies and symptoms which refutes the mistaken tendency to categorize all plantar heel pain singularly as either plantar fasciitis or fasciosis. Recognizing that there is likely an interplay of inflammatory, degenerative, and neuropathic etiologic conditions of this often-difficult malady to treat, a novel injection paradigm of botulinum toxin is explored in the treatment of 4 distinct presentations of Plantar Heel Pain Syndrome with encouraging results. Botulinum toxin injection into two intrinsic foot muscles; Abductor Hallucis and Quadratus Plantae at their origins with electrical stimulation is presented as novel method to treat four distinct etiologies of Plantar Heel Pain Syndrome. This method of botulinum toxin injection resulted in significant prolonged improvement of patient function and pain reduction in four variations of Plantar Heel Pain Syndrome. A precise injection paradigm facilitated with direct intrinsic muscle stimulation of the Abductor Hallucis and Quadratus Plantae at their origins may prove to be effective in reducing the disabilities of Plantar Heel Pain Syndrome and its associated pain.

The differential impact of neuropathic, musculoskeletal and neurovascular orofacial pain on psychosocial function.

While the psychosocial morbidity of orofacial pain (OFP) is widely recognized, the differential impact of musculoskeletal, neuropathic and neurovascular symptoms on pain and psychosocial function in individuals with and without coexisting OFP conditions is unclear. This was a comparative cross-sectional study of 350 consecutive patients attending an OFP clinic; 244 completed standardized self-report measures of pain experience, mood, and generic and oral health-related quality of life (HRQoL). The impact of musculoskeletal, neuropathic and neurovascular symptoms on measures was assessed using linear and logistic generalized linear models. Two hundred patients were diagnosed with a neuropathic condition: 125 with musculoskeletal pain and 101 with (neurovascular) headache disorders. 23% of patients presented with multiple OFP conditions; this was more common in patients with neurovascular (62%) than neuropathic (21%) and/or musculoskeletal orofacial symptoms (28%). Patients with neurovascular symptoms experienced significantly higher levels of pain, evidenced less pain self-efficacy and had poorer overall health. Neuropathic OFP was significantly associated with greater psychological and social oral health disability. Multiple OFP symptoms were not linked to pain severity or psychosocial function, although health scores were worse for patients with neurovascular pain and neuropathic/musculoskeletal symptoms compared with patients with only neurovascular symptoms. The profile and degree of psychosocial morbidity in patients with OFP is significantly related to the types of presenting orofacial symptoms. Patients with neurovascular pain present with higher pain levels and have poorer health while those with neuropathic pain have higher oral functional morbidity; both may require more complex multidisciplinary management.