Generation Of Pain Research Articles

Genetic evidence of the function of Phox2a-expressing anterolateral system neurons in the transmission of chronic pain.

The development of the chronic neuropathic pain state often originates at the level of peripheral sensory neurons, whose abnormal function elicits central sensitization and maladaptive plasticity in the nociceptive circuits of the spinal dorsal horn. These changes eventually reach supraspinal areas bringing about cognitive and affective co-morbidities of chronic pain such as anxiety and depression. This transmission presumably relies on the function of spinal projection neurons at the origin of the anterolateral system (AS). However, the identity of these neurons and the extent of their functional contribution remain unknown. Here, we asked these questions in the context of the mouse AS neurons that require the transcription factor Phox2a for their normal target connectivity and function in transmitting acute nociceptive information to the brain. To this end, we examined the effects of a spinal cord-specific loss of Phox2a (Phox2acKO) on the development of central sensitization evoked by the spared nerve injury (SNI) model of chronic pain. We found that SNI-treated Phox2acKO mice developed normal reflexive spinal responses such as mechanical allodynia evidenced by a decreased withdrawal threshold to von Frey filament stimulation and dynamic brush. On the other hand, Phox2acKO attenuated the development of cold but not mechanical hyperalgesia, in behavioral paradigms that require the relay of nociceptive information to the brain. Furthermore, Phox2acKO attenuated anxio-depressive-like behaviors evoked by SNI, measured by performance in the open field test and tail suspension test. Thus, Phox2a AS neurons play a critical role in the generation and maintenance of chronic neuropathic pain.

Ion channels involved in inflammation and pain in osteoarthritis and related musculoskeletal disorders.

Osteoarthritis (OA) is a currently incurable, chronic, progressive and debilitating musculoskeletal condition. One of its hallmark symptoms is chronic nociceptive and neuropathic pain, which significantly reduces the quality of life of OA patients. While research into the pathomechanisms of OA pain is ongoing and several pain pathways are well understood, the true source of OA pain remains unclear. Ion channels and transporters are key mediators of nociceptive pain. In this narrative review article, we summarize the state-of-the-art in relation to the distribution and function of ion channels in all major synovial joint tissues in the context of pain generation. We provide an update on the ion channels likely involved in mediating peripheral and central nociceptive pathways in the nervous system in OA pain, including voltage-gated sodium and potassium channels, members of the transient receptor potential (TRP) channel family, and purinergic receptor complexes. We focus on ion channels and transporters that have a potential to be candidate drug targets for pain management in OA patients. We propose that ion channels expressed by the cells of constituent tissues of OA-afflicted synovial joints including cartilage, bone, synovium, ligament and muscle, should be more thoroughly investigated and targeted in the context of OA pain. Based on key findings from recent basic research articles as well as clinical trials, we propose novel directions for the development of future analgesic therapies to improve the quality of life of OA patients.

ID: 212609 Spinal Cord Stimulator (SCS) Battery Site Seromas Co-Recurring With Dysuria: A Case Report

A 45-year-old female with low back radicular pain syndrome after a fall injury status post SCS implantation (2016) presents with concomitant pocket site swelling and dysuria. Subacute battery site infection after laminectomy was treated with IV Vancomycin followed by a week course of Doxycycline suppression conferring verified infection resolution. SCS improved the patient’s radicular pain; however, pain to her battery site with dysuria continued. Battery depth as a pain generator was ruled out after readjustment. A seroma was identified in 2020 and symptoms continued to coincide with dysuria with waning severity after antibiotics. Chronic suppressive therapy with Macrobid improved symptoms but symptoms recurred with antibiotic wean. In 2022 the patient presented with battery site abscess concern. She was found to have cystitis though remained afebrile with normal inflammatory markers, no leukocytosis, and negative CT. Ultrasound redemonstrated seroma with an unremarkable aspirate. Ceftriaxone resolved her symptoms. SCS removal was offered but the patient declined due to sustained benefit from SCS.

ID: 208462 Medial Branch Radiofrequency Denervation Improves Pain, Quality-of-Life, and Disability in Patients With Chronic Spinal Pain

Facet joints are clinically important spinal pain generators in 15%-45% of patients with chronic low back pain, 48% with thoracic pain, and 54%-67% with chronic neck pain.1 Radiofrequency (RF) denervation is a minimally invasive procedure that conventionally uses heat generated by radio waves to target peripheral nerves; specifically, the medial branches of the dorsal rami for facetogenic pain. The benefit of RF procedures in the management of chronic low back pain has recently been questioned.2 Broad variations in clinical practice, however, underlined the need for standardization.3 The aim of this abstract is to affirm the role of these techniques in managing chronic spinal pain.

ID: 220389 SCS in Patients Without Options for Corrective Surgery; Results From DISTINCT, a Prospective RCT Trial

Low back pain (LBP) is a highly prevalent, costly condition affecting millions of people worldwide across all sociodemographic classes. Those with an identifiable anatomic pain generator may undergo back surgery and achieve relief, but many are not candidates as they lack an identifiable surgically corrective pathology. Standard non-operative strategies include physiotherapy, oral analgesics, and image guided injections; these may not provide durable relief. Spinal cord stimulation is sometimes used to treat these patients but level I evidence is sparse. We present results from DISTINCT (NCT04479787), the largest RCT to date, comparing passive recharge burst SCS to conventional medical management (CMM) in patients suffering from chronic, refractory axial low back pain, who have not had lumbar spine surgery and for whom corrective surgery is not an option.

Functional Expression of IP, 5-HT4, D1, A2A, and VIP Receptors in Human Odontoblast Cell Line.

Odontoblasts are involved in sensory generation as sensory receptor cells and in dentin formation. We previously reported that an increase in intracellular cAMP levels by cannabinoid 1 receptor activation induces Ca2+ influx via transient receptor potential vanilloid subfamily member 1 channels in odontoblasts, indicating that intracellular cAMP/Ca2+ signal coupling is involved in dentinal pain generation and reactionary dentin formation. Here, intracellular cAMP dynamics in cultured human odontoblasts were investigated to understand the detailed expression patterns of the intracellular cAMP signaling pathway activated by the Gs protein-coupled receptor and to clarify its role in cellular functions. The presence of plasma membrane Gαs as well as prostaglandin I2 (IP), 5-hydroxytryptamine 5-HT4 (5-HT4), dopamine D1 (D1), adenosine A2A (A2A), and vasoactive intestinal polypeptide (VIP) receptor immunoreactivity was observed in human odontoblasts. In the presence of extracellular Ca2+, the application of agonists for the IP (beraprost), 5-HT4 (BIMU8), D1 (SKF83959), A2A (PSB0777), and VIP (VIP) receptors increased intracellular cAMP levels. This increase in cAMP levels was inhibited by the application of the adenylyl cyclase (AC) inhibitor SQ22536 and each receptor antagonist, dose-dependently. These results suggested that odontoblasts express Gs protein-coupled IP, 5-HT4, D1, A2A, and VIP receptors. In addition, activation of these receptors increased intracellular cAMP levels by activating AC in odontoblasts.

Ultrasound-guided intra-sacroiliac joint injection — methylprednisolone versus triamcinolone: a randomized comparative study

BackgroundThe sacroiliac joint (SIJ) has been considered as a pain generator in about 10% to 25% of patients with leg or low back pain. The current study was conducted to compare the effectiveness of ultrasound-guided intra-articular SIJ injection of methylprednisolone versus triamcinolone acetonide according to postinjection pain relief, the random blood glucose (RBG) level in diabetic patients, quality of life (QoL), patient’s satisfaction, and the analgesic requirement.ResultsNRS was better at rest and at motion in MTP groups 3 (2–3) and 4 (3–5) compared to TMC groups 4 (3–5) and 5 (3–6) at 2 weeks after injection with statistically significant difference P equal 0.025 and 0.036, respectively, while there was no statistically significant difference between the studied groups at 1, 2, and 3 months after injection. The RBG level was higher in the MTP group in the 1st, 2nd, and 3rd days after injection 206 (168–308), 245 (200–385), and 215 (179–343) compared to the TMC group 170 (136–271), 168 (119–233), and 166 (110–253) with statistically significant difference P equal 0.066, 0.045, and 0.049, respectively. However, there was no statistically significant difference in the RBG level at baseline, 4th, 5th, 6th, and 7th days after injection between the two studied groups. Moreover, there was a statistically significant elevation in the RBG level within the MTP group in the first 3 days compared to the baseline (P ˂ 0.001). There was no statistically significant difference according to QoL, patient’s satisfaction, and the analgesic requirement between both groups.ConclusionsSIJ injection with methylprednisolone or triamcinolone acetonide showed an improvement in pain score, while the MTP group was better in NRS at 2 weeks. Also, the RBG level in diabetic patients was higher in the MTP group in the 1st, 2nd, and 3rd days after injection. There was upgrading in QoL, similarity in patient’s satisfaction, and reducing the use of analgesia with no statistically significant difference between the studied groups.

Imaging the neural substrate of trigeminal neuralgia pain using deep learning.

Trigeminal neuralgia (TN) is a severe and disabling facial pain condition and is characterized by intermittent, severe, electric shock-like pain in one (or more) trigeminal subdivisions. This pain can be triggered by an innocuous stimulus or can be spontaneous. Presently available therapies for TN include both surgical and pharmacological management; however, the lack of a known etiology for TN contributes to the unpredictable response to treatment and the variability in long-term clinical outcomes. Given this, a range of peripheral and central mechanisms underlying TN pain remain to be understood. We acquired functional magnetic resonance imaging (fMRI) data from TN patients who (1) rested comfortably in the scanner during a resting state session and (2) rated their pain levels in real time using a calibrated tracking ball-controlled scale in a pain tracking session. Following data acquisition, the data was analyzed using the conventional correlation analysis and two artificial intelligence (AI)-inspired deep learning methods: convolutional neural network (CNN) and graph convolutional neural network (GCNN). Each of the three methods yielded a set of brain regions related to the generation and perception of pain in TN. There were 6 regions that were identified by all three methods, including the superior temporal cortex, the insula, the fusiform, the precentral gyrus, the superior frontal gyrus, and the supramarginal gyrus. Additionally, 17 regions, including dorsal anterior cingulate cortex (dACC) and the thalamus, were identified by at least two of the three methods. Collectively, these 23 regions are taken to represent signature centers of TN pain and provide target areas for future studies seeking to understand the central mechanisms of TN.

Subpectoral Biceps Tenodesis Using an All-Suture Knotless Anchor

The long head of the biceps tendon is a common pain generator in the anterior shoulder and is concomitantly seen with other shoulder pathology including subacromial impingement, as well as rotator cuff and labral tears. This Technical Note describes a mini-open onlay biceps tenodesis technique using all-suture knotless anchor fixation. This technique is easily reproducible, is efficient, and offers the unique benefits of providing a consistent length-tension relation and mitigating the risk of peri-implant reaction and fracture without sacrificing strength of fixation.

Modulation of G-protein activation, calcium currents and opioid receptor phosphorylation by the pH-dependent antinociceptive agonist NFEPP.

N-(3-fluoro-1-phenethylpiperidine-4-yl)-N-phenyl propionamide is a newly-designed pain killer selectively activating G-protein-coupled mu-opioid receptors (MOR) in acidic injured tissues, and therefore devoid of central side effects which are typically elicited at normal pH values in healthy tissues. However, the neuronal mechanisms underlying NFEPP's antinociceptive effects were not examined in detail so far. Voltage-dependent Ca2+ channels (VDCCs) in nociceptive neurons play a major role in the generation and inhibition of pain. In this study, we focused on the effects of NFEPP on calcium currents in rat dorsal root ganglion (DRG) neurons. The inhibitory role of the G-protein subunits Gi/o and Gβγ on VDCCs was investigated using the blockers pertussis toxin and gallein, respectively. GTPγS binding, calcium signals and MOR phosphorylation were also investigated. All experiments were performed at acidic and normal pH values using NFEPP in comparison to the conventional opioid agonist fentanyl. At low pH, NFEPP produced more efficient G-protein activation in transfected HEK293 cells and significantly reduced VDCCs in depolarized DRG neurons. The latter effect was mediated by Gβγ subunits, and NFEPP-mediated MOR phosphorylation was pH-dependent. Fentanyl's responses were not affected by pH changes. Our data indicate that NFEPP-induced MOR signaling is more effective at low pH and that the inhibition of calcium channels in DRG neurons underlies NFEPP's antinociceptive actions.

Defining the Patient with Lumbar Discogenic Pain: Real-World Implications for Diagnosis and Effective Clinical Management.

There is an enormous body of literature that has identified the intervertebral disc as a potent pain generator. However, with regard to lumbar degenerative disc disease, the specific diagnostic criteria lack clarity and fail to capture the primary components which include axial midline low back pain with or without non-radicular/non-sciatic referred leg pain in a sclerotomal distribution. In fact, there is no specific ICD-10-CM diagnostic code to classify and define discogenic pain as a unique source of pain distinct from other recognized sources of chronic low back pain including facetogenic, neurocompressive including herniation and/or stenosis, sacroiliac, vertebrogenic, and psychogenic. All of these other sources have well-defined ICD-10-CM codes. Corresponding codes for discogenic pain remain absent from the diagnostic coding vernacular. The International Society for the Advancement of Spine Surgery (ISASS) has proposed a modernization of ICD-10-CM codes to specifically define pain associated with lumbar and lumbosacral degenerative disc disease. The proposed codes would also allow the pain to be characterized by location: lumbar region only, leg only, or both. Successful implementation of these codes would benefit both physicians and payers in distinguishing, tracking, and improving algorithms and treatments for discogenic pain associated with intervertebral disc degeneration.

Evaluation of Effect of Modic Changes on Treatment Outcomes of Nonspecific Low Back Pain Patients Presenting to 501 Hospitals Receiving Conservative Treatments

Background: Modic changes (MC) are among the pain generators in the lumbar spine and could affect back pain treatments. Objectives: The current study aimed to investigate the effect of MC on the treatment outcomes of low back pain (LBP) patients who underwent conservative treatments. Methods: This prospective cohort study was performed on 166 nonspecific LBP patients presenting to 501 Hospital receiving conservative treatments. The patients were categorized based on their MC status, which was determined using a magnetic resonance imaging scan at baseline. Japanese Orthopedic Association (JOA) score was considered a measure of back pain and disability using a valid and reliable questionnaire for each participant. The data were collected on the age, gender, and duration of pain for each participant. The follow-up JOA score was also calculated for each patient after 6-month conservative treatments. The patient was considered improved if the JOA change score was higher than 0. Results: The average baseline JOA score in MC patients was 14.3 (2.2); however, it was 14.4 (2.0) in patients without MC (P = 0.750). After 6-month conservative treatments, the average JOA score reached 16.7 (3.4) and 17.1 (2.9) in patients with and without MC, respectively. No statistically significant difference was observed in this regard (P = 0.540). The proportion of improved cases was 70.7%, 82.8%, 63.4%, and 50.0% in no MC, MC type I, MC type II, and MC type III, respectively, with no statistically significant difference among the groups (P = 0.561). Conclusions: A 6-month conservative treatment was a safe and effective approach to improving the clinical condition of patients with LBP. However, there was no association between the presence of MC or any specific type of MC and treatment outcomes.

Initial Validation of a Sacroiliac Joint-Specific Disability Questionnaire.

Low back pain is a multidimensional disorder that can originate from a variety of pain generators, including the sacroiliac (SI) joint. Although the Oswestry Disability Index (ODI) is often used in SI joint treatment studies, the effects of the SI joint on functional disability are likely different from those of other low back pain generators. Thus, we developed the Denver SI Joint Questionnaire (DSIJQ) and performed validation testing in patients (n=24) with SI joint-specific pain at baseline, +2 weeks, and +6 months. Psychometric analyses included test-retest reliability, internal consistency, content validity, convergent criterion validity, divergent criterion validity, and responsiveness. The DSIJQ showed good test-retest reliability (intraclass correlation coefficient=0.87), internal consistency (Cronbach's alpha=0.842), content validity (<30% floor/ceiling effects), convergent criterion validity (r=0.89; P<.001), and divergent criterion validity (r=-0.33; P=.12). The DSIJQ was correlated with performance on two physical function tests: Timed Upand-Go (r=0.53; P=.008) and 5 Minute Walk (r=-0.52; P=.009). The DSIJQ showed better responsiveness than the ODI (standardized response mean and effect size, 1.14 and 1.45 for DSIJQ and 0.75 and 0.81 for ODI). Overall, the DSIJQ performed well on all psychometrics. Importantly, we validated the DSIJQ with patients' ability to complete two tests of physical functioning. Moreover, the DSIJQ was more sensitive to changes in SI joint disability than the ODI. These psychometrics suggest the DSIJQ is appropriate for evaluating SI joint disability and detecting changes in disability after targeted SI joint treatment. [Orthopedics. 2023;46(6):345-351.].

Personalized Interventional Surgery of the Lumbar Spine: A Perspective on Minimally Invasive and Neuroendoscopic Decompression for Spinal Stenosis.

Pain generator-based lumbar spinal decompression surgery is the backbone of modern spine care. In contrast to traditional image-based medical necessity criteria for spinal surgery, assessing the severity of neural element encroachment, instability, and deformity, staged management of common painful degenerative lumbar spine conditions is likely to be more durable and cost-effective. Targeting validated pain generators can be accomplished with simplified decompression procedures associated with lower perioperative complications and long-term revision rates. In this perspective article, the authors summarize the current concepts of successful management of spinal stenosis patients with modern transforaminal endoscopic and translaminar minimally invasive spinal surgery techniques. They represent the consensus statements of 14 international surgeon societies, who have worked in collaborative teams in an open peer-review model based on a systematic review of the existing literature and grading the strength of its clinical evidence. The authors found that personalized clinical care protocols for lumbar spinal stenosis rooted in validated pain generators can successfully treat most patients with sciatica-type back and leg pain including those who fail to meet traditional image-based medical necessity criteria for surgery since nearly half of the surgically treated pain generators are not shown on the preoperative MRI scan. Common pain generators in the lumbar spine include (a) an inflamed disc, (b) an inflamed nerve, (c) a hypervascular scar, (d) a hypertrophied superior articular process (SAP) and ligamentum flavum, (e) a tender capsule, (f) an impacting facet margin, (g) a superior foraminal facet osteophyte and cyst, (h) a superior foraminal ligament impingement, (i) a hidden shoulder osteophyte. The position of the key opinion authors of the perspective article is that further clinical research will continue to validate pain generator-based treatment protocols for lumbar spinal stenosis. The endoscopic technology platform enables spine surgeons to directly visualize pain generators, forming the basis for more simplified targeted surgical pain management therapies. Limitations of this care model are dictated by appropriate patient selection and mastering the learning curve of modern MIS procedures. Decompensated deformity and instability will likely continue to be treated with open corrective surgery. Vertically integrated outpatient spine care programs are the most suitable setting for executing such pain generator-focused programs.

Gluteus Maximus Transfer for Hip Abductor Deficiency

Hip abductor deficiency resulting from gluteus medius and minimus pathology is increasingly recognized as a generator of lateral-sided hip pain. In the setting of a failed gluteus medius repair or in patients with irreparable tears, transfer of the anterior portion of the gluteus maximus muscle can be performed to treat gluteal abductor deficiency. The classic description of the gluteus maximus transfer technique relies solely on bone tunnel fixation. This article describes a reproducible technique that incorporates the addition of a distal row to the tendon transfer, which may improve fixation by both compressing the tendon transfer to the greater trochanter and providing improved biomechanical strength to the transfer.

From non-specific low back pain to chronic primary musculoskeletal low back pain: the evolving concept

Background: Low back pain (LBP) for many years is considered one of the most common conditions causing work absenteeism and long-term disability, with important implications for public health systems and economies. Pain generators of LBP are various, being distinguished specific and non-specific causative mechanisms. The term “non-specific” LBP remains ambiguous as potential sources of pain are supposed to be muscles or joints, but supplementary investigations do not correlate enough to explain the pain intensity and disability. The nociceptive and/or neuropathic mechanisms characteristic for acute pain tend to be influenced by central sensitization while pain chronification occurs, leading to new descriptor as nociplastic pain. Chronic low back pain, considered mostly non-specific, was mechanistically referred to primary musculoskeletal low back pain, the concept introduced in the new ICD-11 classification. The process of acceptance by the scientific medical community raised debates and discussions. The aim of the study was to analyze the evolving concept of non-specific low back pain to chronic primary musculoskeletal low back pain. A narrative literature review was carried out. Conclusions: The term non-specific low back pain is used when the pain generators have not been accurately determined or cannot fully explain the existing symptomatology. Chronic primary musculoskeletal low back pain is better explained by central sensitization mechanisms and altered nociception, named nociplastic pain. Because of raised ambiguities regarding this concept further studies are expected to shed light on the problem.

Complete Resolution of Refractory Axial Low Back Pain After Myomectomy.

We present a case of a 39-yr-old woman with a 3-mo history of axial low back pain who was found to have a 3.8-cm uterine fibroid, which was initially thought to be an incidental finding. Her low back pain failed to respond to conservative management, and she was eventually referred to gynecology. Her pain subsequently resolved after myomectomy. To the best of our knowledge, complete resolution of low back pain after myomectomy has not been previously described in the literature. Although uterine fibroids are commonly noted on imaging, they are often ignored. We encourage clinicians to consider fibroids as pain generators, especially when treating patients with refractory axial low back pain.

Redefining the Classification for Bertolotti Syndrome: Anatomical Findings in Lumbosacral Transitional Vertebrae Guide Treatment Selection

We present the Jenkins classification for Bertolotti syndrome or symptomatic lumbosacral transitional vertebra (LSTV) and compare this with the existing Castellvi classification for patients presenting for treatment. We performed a retrospective cohort study of 150 new patients presenting for treatment of back, hip, groin, and/or leg pain from July 2012 through February 2022. Using magnetic resonance imaging, computed tomography, and radiography, the patients with a radiographic finding of LSTV, an appropriate clinical presentation, and identification of LSTV as the primary pain generator via diagnostic injections were diagnosed with Bertolotti syndrome. Patients for whom conservative treatment had failed and who underwent surgery to address their LSTV were included in the present study. The Castellvi classification excludes 2 types of anatomic variants: the prominent anatomic side and the potential transverse process and iliac crest contact. Of 150 patients with transitional anatomy, 103 (69%) were identified with Bertolotti syndrome using the Jenkins classification and received surgery (46 men [45%] and 57 women [55%]). Of the 103 patients, 90 (87%) underwent minimally invasive surgery. The patients presented with pain localized to the back (n= 101; 98%), leg (n= 79; 77%), hip (n= 51; 49%), and buttock (n= 52; 50%). Only 84 of the Jenkins classification patients (82%) met any of the Castellvi criteria. All 19 patients for whom the Castellvi classification failed had had type 1 anatomy using the Jenkins system and underwent surgery (decompression, n= 16 [84%]; fusion, n= 1 [5%]; fusion plus decompression, n= 2 [11%]). Of these 19 patients, 17 (89%) had improved pain scores. The 19 patients exclusively diagnosed via the Jenkins classification had no significant differences in improved pain compared with those diagnosed using the Castellvi classification. The Jenkins classification improves on the prior Castellvi classification to more comprehensively describe the functional anatomy, identify uncaptured anatomy, and better predict optimal surgical procedures to treat those with Bertolotti syndrome.

A17 EVIDENCE OF PROTEASE-MEDIATED PRO-NOCICEPTIVE EFFECTS OF FECAL SUPERNATANTS FROM CROHN'S DISEASE PATIENTS

Abstract Background Abdominal pain is a debilitating symptom of Crohn’s disease (CD). Despite the current treatment options for this disease, abdominal pain is an unresolved problem that commonly persists in the absence of active inflammation. This suggests that something other than inflammation is driving the pain during the quiescent phase. We have previously reported that microbial proteases can directly modulate the excitability of dorsal root ganglia (DRG) neurons, many of which are pain-sensing. We hypothesize that luminal proteases of CD patients are contributing to their abdominal pain. Purpose Determine whether luminal mediators in CD fecal samples induce changes in pain signalling. Method The effects of patient (active CD [n = 3] and healthy volunteer (HV) [n = 3]) fecal supernatant (FS) samples on pain-sensing neurons were assessed using ex-vivo single unit afferent nerve recordings from mouse colons. Each sample was tested in colonic preparations from a least 5 mice. To further examine cellular mechanisms, DRG neurons were isolated and incubated overnight in media containing CD FS or HV FS media. Changes in neuronal excitability were recorded by determining the rheobase (lower rheobase=increased excitability) using patch clamp recordings (n ≥ 9 DRG neurons/group). Protease inhibitors were applied in both bioassays to determine whether these inhibited the excitatory effect of FS. Lastly, total proteolytic activity in the CD and HV fecal samples was calculated using a casein colorimetric protease detection assay. Result(s) FS from HV had no effect on afferent nerve excitability (p = 0.8920). FS from active CD patients increased action potential discharge from colonic afferent nerves by 85% (p&amp;lt;0.0001) and selectively increased the activation of high-threshold units, which are putative nociceptors, by 44% (p=0.0074). A protease inhibitor cocktail (1:1000) and protease-activated receptor (PAR)-2 antagonist GB83 (10µM) both blocked the excitatory effects of CD FS (p&amp;lt;0.05). Overnight incubation with CD FS also had an excitatory effect on DRG neurons compared to HV FS (rheobase decreased by 46%, p&amp;lt;0.05). The effect of CD FS was blocked by GB83 (10µM) (p&amp;lt;0.001) and a serine protease inhibitor (FUT175; 100µM) (p&amp;lt;0.05) independently, but the activity was not blocked by E64 (30nM) a cysteine protease inhibitor. A 200-fold increase (p&amp;lt;0.0001) in total proteolytic activity was found in CD FS compared to HV FS. Conclusion(s) Luminal serine proteases, but not cysteine proteases, appear to be driving nociceptive signalling in CD patients. This provides insight into the generation of pain in CD patients and may be a potential target to mitigate this action. Further research is required to elucidate whether these pro-nociceptive proteases are of bacterial or host origin and their effects in the quiescent phase. Disclosure of Interest None Declared

Effects of a Myofascial Technique on the Stiffness and Thickness of the Thoracolumbar Fascia and Lumbar Erector Spinae Muscles in Adults with Chronic Low Back Pain: A Randomized before-and-after Experimental Study.

The thoracolumbar fascia (TLF) may be a pain generator, given its rich innervation. Structural and biomechanical changes have also been documented in adults with chronic non-specific low back pain (LBP). Myofascial techniques (MFTs) are commonly used in manual therapy and are hypothesized to reduce tissue stiffness and pain. However, evidence for these effects is limited. The objective of this study was to evaluate the immediate effects of a standardized MFT compared to a simulated MFT on: (1) the stiffness of the TLF and erector spinae muscles (shear-wave sonoelastography), (2) the thickness of the TLF (B-mode ultrasound), and (3) pain intensity (numerical rating scale). Forty-nine participants with chronic non-specific LBP were included in a randomized before-and-after experimental study. Outcome measures were collected before (T0) and immediately after the intervention (T1). Pain intensity was also assessed on day two (T2) and seven (T7). The MFT group showed a significant decrease in left erector spinae muscle stiffness and left TLF thickness compared to the simulated group. In addition, there was a significant reduction in pain intensity in the MFT group compared to the simulated group at T1 and T2. The results of this study suggest that MFT results in immediate tissue changes and transient pain reduction in patients with LBP.