Selective Targeting of Serotonin 5-HT1a and 5-HT3 Receptors Attenuates Acute and Long-Term Hypersensitivity Associated With Neonatal Procedural Pain.

Neonatal painful procedures causes acute pain and trigger long-term changes in nociceptive processing and anxiety behavior, highlighting the need for adequate analgesia during this critical time. Spinal serotonergic receptors 5-HT1a and 5-HT3 play an important role in modulating incoming nociceptive signals in neonates. The current study aims to attenuate acute and long-term hypersensitivity associated with neonatal procedural pain using ondansetron (a 5-HT3 antagonist) and buspirone (a 5-HT1a agonist) in a well-established rat model of repetitive needle pricking.

Anatomical changes in descending serotonergic projections from the rostral ventromedial medulla to the spinal dorsal horn following repetitive neonatal painful procedures.

Excessive noxious stimulation during the critical neonatal period impacts the nociceptive network lasting into adulthood. As descending serotonergic projections from the rostral ventromedial medulla (RVM) to the spinal dorsal horn develop postnatally, this study aims to investigate the long-term effect of repetitive neonatal procedural pain on the descending serotonergic RVM-spinal dorsal horn network. A well-established rat model of repetitive noxious procedures is used in which neonatal rats received four noxious needle pricks or tactile stimulation with a cotton swab per day in the left hind paw from day of birth to postnatal Day 7.

Neonatal procedural pain affects state, but not trait anxiety behavior in adult rats.

The influence of neonatal experiences upon later-life affective behavior is increasingly recognized, but the reported effects on anxiety are often contradictory. The observed effect may depend upon the type of anxiety (state or trait) affected. The current study aims to investigate whether neonatal repetitive needle pricking alters anxiety behavior in adulthood, by assessing both state and trait anxiety in rats.

The development of descending serotonergic modulation of the spinal nociceptive network: a life span perspective.

The nociceptive network, responsible for transmission of nociceptive signals that generate the pain experience, is not fully developed at birth. Descending serotonergic modulation of spinal nociception, an important part of the pain network, undergoes substantial postnatal maturation and is suggested to be involved in the altered pain response observed in human newborns. This review summarizes preclinical data of the development of descending serotonergic modulation of the spinal nociceptive network across the life span, providing a comprehensive background to understand human newborn pain experience and treatment.

The Diagnostic Value of an X-ray-based Scoring System for Degeneration of the Cervical Spine: A Reproducibility and Validation Study.

Background: In interventional pain medicine, cervical facet joint (CFJ) pain is commonly treated with CFJ denervation techniques, almost automatically assuming degeneration of the CFJs as an important cause of CFJ pain. A standard cervical X-ray is still commonly used in the clinical evaluation of patients suspected for CFJ degeneration. Although degenerative features can be visualized by different radiological imaging techniques, the relation between radiological degenerative features of the cervical spine and pain remains controversial.

Efficacy and Long-term Effect of Radiofrequency Denervation in Patients with Clinically Diagnosed Cervical Facet Joint Pain: A Double-blind Randomized Controlled Trial.

Study Design: Multicenter double-blind randomized sham-controlled trial.

Objective: To assess the efficacy of radiofrequency (RF) denervation of the cervical facet joints in chronic cervical facet joint pain.

Summary Of Background Data: One randomized controlled trial showed efficacy of RF denervation in whiplash-associated disease.

Methadone effectively attenuates acute and long-term consequences of neonatal repetitive procedural pain in a rat model.

Background: Painful procedures in early life cause acute pain and can alter pain processing at a spinal level lasting into adulthood. Current methods of analgesia seem unable to prevent both acute and long-term hypersensitivity associated with neonatal pain. The current study aims to prevent acute and long-term hypersensitivity associated with neonatal procedural pain using methadone analgesia in rat pups.

Qualitative review on N-methyl-D-aspartate receptor expression in rat spinal cord during the postnatal development: Implications for central sensitization and pain.

The N-methyl-D-aspartate receptor (NMDAR) is an important mediator of central sensitization and nociception in the rat spinal dorsal horn. The NMDAR subunits and splice variants determine the properties of the receptor. Understanding the expression of NMDAR subunits in spinal cord during the neonatal development is important as it may have consequences for the process of central sensitization and nociception in later life.

Repetitive noxious stimuli during early development affect acute and long-term mechanical sensitivity in rats.

Background: Prematurely born infants are frequently exposed to painful procedures in the neonatal intensive care unit, causing changes to the development of the nervous system lasting into adulthood. The current study aims to study acute and long-term consequences of neonatal repetitive noxious stimulation.

Methods: Rat pups received either 4 or 10 unilateral needle pricks per day, while control littermates received 4 or 10 tactile stimuli in the first postnatal week.

Repeated touch and needle-prick stimulation in the neonatal period increases the baseline mechanical sensitivity and postinjury hypersensitivity of adult spinal sensory neurons.

Noxious stimulation at critical stages of development has long-term consequences on somatosensory processing in later life, but it is not known whether this developmental plasticity is restricted to nociceptive pathways. Here, we investigate the effect of repeated neonatal noxious or innocuous hind paw stimulation on adult spinal dorsal horn cutaneous mechanical sensitivity. Neonatal Sprague-Dawley rats of both sexes received 4 unilateral left hind paw needle pricks (NPs, n = 13) or 4 tactile (cotton swab touch) stimuli, per day (TC, n = 11) for the first 7 days of life.

Adult spinal opioid receptor μ1 expression after incision is altered by early life repetitive tactile and noxious procedures in rats.

Clinical and experimental data suggests that noxious stimulation at critical stages of development results in long-term changes on nociceptive processing in later life. Here, we use an established, well-documented rat model of repetitive noxious procedures closely mimicking the clinical situation in the NICU. In order to understand molecular changes underlying the long-term consequences of repetitive stimulation of the developing nociceptive system the present study aims to analyze the presence of the µ-opioid-receptor-1 (OPRM1).

Neonatal Plasticity of the Nociceptive System: Mechanisms, Effects, and Treatment of Repetitive Painful Procedures During NICU Admittance.

Introduction: In the Neonatal Intensive Care Unit (NICU), prematurely born infants undergo a range of skin breaking and painful procedures. At the same time, the spinal nociceptive system is in a sensitive developmental stage. Both neonatal repetitive painful procedures and their treatment can induce plasticity of the neonatal spinal nociceptive system, causing long-lasting alterations to pain processing and pain reactivity.

A Modified Posterolateral Approach for Radiofrequency Denervation of the Medial Branch of the Cervical Segmental Nerve in Cervical Facet Joint Pain Based on Anatomical Considerations.

The cervical facet joints, also called the zygapophyseal joints, are a potential source of neck pain (cervical facet joint pain). The cervical facet joints are innervated by the cervical medial branches (CMBs) of the cervical segmental nerves. Cervical facet joint pain has been shown to respond to multisegmental radiofrequency denervation of the cervical medial branches.

Neonatal paracetamol treatment reduces long-term nociceptive behaviour after neonatal procedural pain in rats.

Background: Pain from skin penetrating procedures (procedural pain) during infancy in the neonatal intensive care unit (NICU) may result in changes of nociceptive sensitivity in later life. This supports the need for pain management during such vulnerable periods in life. This study, therefore, analyses the short- and long-term consequences of neonatal paracetamol (acetaminophen) treatment on pain behaviour in an experimental rat model of neonatal procedural pain.

Predictive Factors for Successful Outcome of Pulsed Radiofrequency Treatment in Patients with Intractable Lumbosacral Radicular Pain.

Background: In a previous prospective study on pulsed radiofrequency (PRF) treatment adjacent to the lumbar dorsal root ganglion (DRG) for patients with chronic lumbosacral radicular pain, we reported success in 55.4% of the patients at 6 months. Identification of predictors for success after PRF may improve outcome.

First Dutch Consensus of Pain Quality Indicators for Pain Treatment Facilities.

Background: There is a general consensus about the need to define and improve the quality of pain treatment facilities. Although guidelines and recommendations to improve the quality of pain practice management have been launched, provision of appropriate pain treatment is inconsistent and the quality of facilities varies widely. The aim of the study was to develop an expert-agreed list of quality indicators applicable to pain treatment facilities.

Pain treatment facilities: do we need quantity or quality?

Rationale, Aims And Objectives: Chronic pain patients referred to a pain treatment facility have no guarantee that they will receive a proper diagnostic procedure or treatment. To obtain information about organizational aspects of pain treatment facilities and the content of their daily pain practice, we performed a questionnaire survey. The aim of the study was to evaluate the amount of pain treatment facilities, the content of organized specialized pain care and adherence to the criteria of the internationally accepted guidelines for pain treatment services.

Pain prevalence and its determinants after spinal cord injury: a systematic review.

Pain prevalence studies are important as they illustrate the magnitude of pain problems in a certain patient population, such as patients living with a spinal cord injury (SCI). Strikingly, reported pain prevalence rates in SCI patients are found to vary greatly, while determinants for the differences between pain prevalence reports remain unclear. We here aim to identify determinants for the differences (heterogeneity) in pain prevalence reports through a systematic review of all SCI pain prevalence reporting studies.

Pulsed radiofrequency: a review of the basic science as applied to the pathophysiology of radicular pain: a call for clinical translation.

Radicular pain is an important health care problem, with only limited evidence-based treatments available. Treatment selection should ideally target documented pathophysiological pathways. In herniated discs, a sequence in the inflammatory cascade can be observed that initiates and maintains increased nociceptive signal input.

Can we "predict" long-term outcome for ambulatory transcutaneous electrical nerve stimulation in patients with chronic pain?

Background: Evidence for effectiveness of transcutaneous electrical nerve stimulation (TENS) is still inconclusive. As heterogeneity of chronic pain patients might be an important factor for this lack of efficacy, identifying factors for a successful long-term outcome is of great importance.

Methods: A prospective study was performed to identify variables with potential predictive value for 2 outcome measures on long term (6 months); (1) continuation of TENS, and (2) a minimally clinical important pain reduction of ≥ 33%.

Prolonged QT interval by methadone: relevance for daily practice? A prospective study in patients with cancer and noncancer pain.

Introduction: Increased methadone use in patients with pain has raised concerns that the effect of methadone on the QT interval duration and the potential risk of torsades de pointes (TdP) has been underestimated. Most studies on prolonged QT intervals by methadone are performed in maintenance patients; however, doses of methadone in pain treatment are much lower. Hardly any studies have prospectively addressed QT interval prolongation by methadone in patients with pain, and this study aims to address this literature gap.

Perinatal maternal stress and serotonin signaling: effects on pain sensitivity in offspring.

It has been estimated that 20% of pregnant women are facing perinatal stress and depression. Perinatal maternal stress has been shown to increase pain sensitivity in offspring. For the treatment of their depressive symptoms, pregnant women are frequently prescribed selective serotonin reuptake inhibitors (SSRIs).

Ultrasonography of the cervical spine: an in vitro anatomical validation model.

Background: Anatomical validation studies of cervical ultrasound images are sparse. Validation is crucial to ensure accurate interpretation of cervical ultrasound images and to develop standardized reliable ultrasound procedures to identify cervical anatomical structures. The aim of this study was to acquire validated ultrasound images of cervical bony structures and to develop a reliable method to detect and count the cervical segmental levels.