Chronic Pregabalin Treatment Ameliorates Pain, but not Depressive-Like Behaviors, in a Reserpine-Induced Myalgia Model in Rats.

BACKGROUND: Anticonvulsants are often prescribed as coanalgesics for pathologies presenting chronic pain, such as chronic neuropathic pain and fibromyalgia. These pathologies are associated with a wide range of comorbidities: chronic fatigue, cognitive impairment, sleep disturbances, and mood disorders. Pregabalin, an anticonvulsant used to treat fibromyalgia syndrome, has been proven to improve pain and fatigue symptoms. However, most studies have not considered the analytic effect of this drug on comorbid depressive-like symptoms in this syndrome. OBJECTIVES: The main study objective was to examine the role of pregabalin in depressive symptomatology comorbid to chronic widespread pain using a reserpine-induced myalgia model. STUDY DESIGN: A randomized, controlled, animal study. SETTING: Research and data analyses were performed at the GESADA laboratory, Department of Human Anatomy and Embryology, University of Valencia, Spain. METHODS: Forty-six Sprague-Dawley male rats were used. Acute chronic pregabalin administration was tested for depressive-like behaviors (Forced Swimming and Novelty-Suppressed Feeding Tests) and for alteration of pain thresholds (tactile allodynia, Electronic Von Frey test; and mechanical hyperalgesia, Randall and Selitto test). The same procedures were followed with duloxetine as a positive control. RESULTS: Pregabalin significantly improved depressive-like behaviors in acute, but not chronic treatment, and significantly ameliorated pain thresholds. LIMITATIONS: Lack of histological and electrophysiological tests. CONCLUSIONS: Pregabalin is not effective in depressive-like symptoms associated with chronic pain but might play an acute antidepressive-like role given its antinociceptive effect.

Health outcomes and costs in patients with osteoarthritis and chronic pain treated with opioids in Spain: the OPIOIDS real-world study.

OBJECTIVE: The objective of this study was to analyze health outcomes, resource utilization, and costs in osteoarthritis patients with chronic nociceptive pain who began treatment with an opioid in real-world practice in Spain. METHODS: We designed a non-interventional, retrospective, longitudinal study with 36 months of follow-up using electronic medical records (EMRs) from primary care centers, of patients aged 18+ years who began a new treatment with an opioid drug in usual practice for chronic pain due to osteoarthritis. Health/non-health resource utilization and costs, treatment adherence, pain change, cognitive functioning, and dependence for basic activities of daily living (BADL) were assessed. RESULTS: A total of 38,539 EMRs [mean age (SD); 70.8 (14.3) years, 72.3% female; 53.3% hip/knee, 25.0% spine, and 21.7% other sites] were recruited. A total of 19.1% of patients remained on initial opioid at 36 months, without significant differences by osteoarthritis site (p = 0.125). Mean total adjusted cost was €17,915, with 27.7% corresponding to healthcare resources and 72.3% to lost productivity. Hospital admissions for osteoarthritis-related surgical interventions accounted for 15.8% of total healthcare cost. A slight mean pain reduction was observed: -1.3 points, -16.9%, p < 0.001, with increases in cognitive deficit (+3.3%, p < 0.001) and moderate to total dependence for BADL (+15.6%, p < 0.001) in a median duration of opioid use of 203 days (IQR: 89-696). CONCLUSIONS: In real-world practice in Spain, opioid use in osteoarthritis was high, but with low adherence. There were meaningful increases in resource use and costs for the National Health System. Pain reduction was modest, whereas cognitive impairment and dependence for BADL increased significantly.

Microscopic Study of Injectable Steroids: Effects of Postmixing Time on Particle Aggregation.

BACKGROUND: Epidural steroid injection (ESI) is a common practice for pain treatment since 1953. In 2014, the FDA issued a warning about ESI. Studies have focused on the effect of the particle size and their ability to generate harmful aggregates. Although steroid aggregates provide longer times for reabsorption, therefore a longer anti-inflammatory effect, they are potentially harmful to the central nervous system via embolic mechanisms.Previous studies have established that steroidal aggregates with asizes over 100 mu m are potentially able to occlude blood vessels. Studies by Tiso et al and Benzon et al addressed the role of steroids on CNS adverse events, with similar outcomes. The main difference was on the role of aggregates with a size over 100 mu m, which Benzon et al. attributed to the ability of certain steroid preparations to rapidly precipitate and form large aggregates. OBJECTIVES: Studying the effect of the time elapsed between mixing the steroid preparation and injection on the number and size of aggregates with sizes above 100 mu m. STUDY DESIGN: Original study in basic science. SETTING: Basic scienceMETHODS: Steroids evaluated are commonly used in Spain for ESI: betamethasone, triamcinolone, and dexamethasone. The size and number of the aggregates was determined for undiluted commercial steroid preparations in the usual amount for a single and double dosage used for ESI.Samples were examined with a Leica TCS-SP2 microscope at the first, the fifth and the 30th minute after shaking the preparations. Aggregates observed in the different preparations were manually counted and grouped in the following size range: 0-20, 20-50, 50-100, 100-300, 300-500 and > 500 mu m.Statistical analysis was carried out using the R software. Nonparametric techniques were used in the comparison of aggregate size. Global comparison of the groups using the Kruskal-Wallis test and post-hoc comparisons using the Wilcoxon test, adjusting P-values by the Holm method for multiple comparisonsRESULTS: Aggregates present in triamcinolone and betamethasone samples were statistically larger than in dexamethasone samples. Triamcinolone suspensions produced significantly larger aggregates than betamethasone five minutes after mixing. Triamcinolone preparations produced greater particle aggregates (> 500 mu m), which were not present in dexamethasone and betamethasone preparations. LIMITATIONS: Study how the human internal factors like blood elements and spinal fluid could interact with steroids and influence the size of the aggregates formed. CONCLUSIONS: This study demonstrates that the size of the particles injected depends on the type of steroid and the time allowed between mixing and injecting. The results demonstrate that waiting longer than 5 minutes between mixing and injecting can predispose the formation of potentially harmful aggregates in triamcinolone and betamethasone samples. The presence of greater particle aggregates (> 500 mu m) may occlude some important vessels and arteries with serious adverse results. Vigorous shaking of the injectable could prevent such events. KEY WORDS: Epidural steroid injection, triamcinolone, betamethasone, dexamethasone, steroid aggregates.

Glia to neuron ratio in the posterior aspect of the human spinal cord at thoracic segments relevant to spinal cord stimulation.

Spinal cord stimulation (SCS) applied between T8 and T11 segments has been shown to be effective for the treatment of chronic pain of the lower back and limbs. However, the mechanism of the analgesic effect at these medullary levels remains unclear. Numerous studies relate glial cells with development and maintenance of chronic neuropathic pain. Glial cells are electrically excitable, which makes them a potential therapeutic target using SCS. The aim of this study is to report glia to neuron ratio in thoracic segments relevant to SCS, as well as to characterize the glia cell population at these levels. Dissections from gray and white matter of posterior spinal cord segments (T8, T9, intersection T9/T10, T10 and T11) were obtained from 11 human cadavers for histological analyses. Neuronal bodies and glial cells (microglia, astrocytes and oligodendrocytes) were immunostained, microphotographed and counted using image analysis software. Statistical analyses were carried out to establish significant differences of neuronal and glial populations among the selected segments, between the glial cells in a segment, and glial cells in white and gray matter. Results show that glia to neuron ratio in the posterior gray matter of the human spinal cord within the T8-T11 vertebral region is in the range 11 : 1 to 13 : 1, although not significantly different among vertebral segments. Glia cells are more abundant in gray matter than in white matter, whereas astrocytes and oligodendrocytes are more abundant than microglia (40 : 40 : 20). Interestingly, the population of oligodendrocytes in the T9/T10 intersection is significantly larger than in any other segment. In conclusion, glial cells are the predominant bodies in the posterior gray and white matter of the T8-T11 segments of the human spinal cord. Given the crucial role of glial cells in the development and maintenance of neuropathic pain, and their electrophysiological characteristics, anatomical determination of the ratio of different cell populations in spinal segments commonly exposed to SCS is fundamental to understand fully the biological effects observed with this therapy.

Cervical plexus as anatomical target for the treatment of postoperative cervical neuropathic pain.

Objective: The incidence of chronic neuropathic pain following neck dissections is approximately 40%. Standard drug therapy in these patients include pharmacologic treatments due to the neuropathic pain (gabapentinoids, tricyclic antidepressants…). In this case, standard options were limited. The addition of ultrasound guidance to invasive pain management techniques has enabled us to successfully treat pathologies in which previous treatments options had been limited. Pulsed radiofrequency (PRF) ablation permits treatment over nerve structures that, due to either their morphological or functional characteristics, could not be approached using the conventional variant. Case report: A 45-year-old man with severe postoperative pain after undergoing partial glossectomy and functional neck dissection for squamous cell carcinoma of the tongue. The patient had been treated pharmacologically for several years with minimal results, baseline VAS of 90. After a successful superficial cervical plexus block under ultrasound guidance, he underwent PRF for a possible long-lasting effect. VAS post PRF improved in subsequent visits: VAS at 1 month was 0; at 3 months was 10 and at 6 months was 60. Conclusion: Postoperative changes to include alterations in nerve structures are a frequent source of chronic pain. The incidence of this type of pain in the cervical region is quite variable. Noninvasive treatment options are limited and oftentimes ineffective. Due to its location, superficial cervical plexus is an anatomical site with the potential risk of undergoing structural alterations (fibrosis, radiotherapy-associated retraction phenomena or neuroma formation). Interventional treatments performed under ultrasound guidance allow the dynamic application of therapies such as radiofrequency ablation. PRF could potentially cause an additive effect between neuromodulation and the hydrodissection caused by the infiltration of substances within a fibrotic area.

Anatomic and Ultrasonographic Evaluation of the Knee Sensory Innervation: A Cadaveric Study to Determine Anatomic Targets in the Treatment of Chronic Knee Pain.

BACKGROUND AND OBJECTIVES: Osteoarthrosis is a main cause of knee pain in the elderly. Pain associated with this condition is often refractory to conservative treatment. Total knee replacement may be the best option for severe pathologies; however, the occurrence of a chronic pain state after knee replacement has been well documented in the literature. The previous descriptions of the genicular nerves have been considered somewhat inaccurate. This innervation is complex and exhibits significant interindividual variability. A precise description of these nerves will increase our knowledge on different patterns and targets, to guide treatment and improve outcomes. The objective of this study was to determine sensory innervation patterns of the knee joint and correlate them with dynamic visualization via ultrasound imaging. METHODS: Systematic cadaveric dissections were performed to determine different patterns of sensory innervation of the knee followed by ultrasonographic correlation. A short-axis ultrasound view of the nerves was used to inject India ink at several points along their course to facilitate the anatomic dissection and confirm their location among adjacent structures. RESULTS: The visualized structures were the following: infrapatellar branch of the saphenous nerve, the branches to vastus medialis, intermedius, and lateralis muscles; obturator nerve; and lateral retinacular and recurrent peroneal nerves. CONCLUSIONS: We conclude that reproducible correlations showing the sensory innervations for the knee are linked to muscular structures. However, high variability among individuals makes it difficult to predict their paths. Our systematic approach, using direct visualization via ultrasound, allows a more accurate placement of the needle for therapeutic purposes.