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. Sprague-Dawley rat pups of both sexes received ondansetron (3 mg/kg), buspirone (3 mg/kg) or saline prior to repetitive needle pricks into the left hind-paw from postnatal day 0-7. Control animals received tactile stimulation or were left undisturbed. Acute, long-term, and post-operative mechanical sensitivity as well as adult anxiety were assessed. Neonatal 5-HT1a receptor agonism completely reverses acute hypersensitivity from P0-7. The increased duration of postoperative hypersensitivity after re-injury in adulthood is abolished by 5-HT3 receptor antagonism during neonatal repetitive needle pricking, without affecting baseline sensitivity. Moreover, 5-HT1a and 5-HT3 receptor modulation decreases adult state anxiety. Altogether, our data suggests that targeted pharmacological treatment based on the modulation of spinal serotonergic network via the 5-HT1a and 5-HT3 receptors in neonates may be of use in treatment of neonatal procedural pain and its long-term consequences. This may result in a new mechanism-based therapeutic venue in treatment of procedural pain in human neonates.

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. Control animals were left undisturbed. When animals reached adulthood, tissue was collected for quantitative immunohistochemical analysis of serotonin (5-hydroxytryptamine, 5-HT) in the RVM and spinal dorsal horn. Both repetitive noxious and tactile procedures in the neonate decreased the 5-HT staining intensity in the adult ipsilateral but not contralateral spinal dorsal horn. Repetitive neonatal noxious procedures resulted in an increased area covered with 5-HT staining in the adult RVM ipsilateral to the side of injury, whereas repetitive neonatal tactile stimulation resulted in increased 5-HT staining intensity in both the ipsi- and contralateral RVM. The number of 5-HT cells in adult RVM is unaffected by neonatal conditions. This detailed anatomical study shows that not only neonatal noxious procedures but also repetitive tactile procedures result in long-lasting anatomical changes of the descending serotonergic system within the RVM and spinal dorsal horn. Future studies should investigate whether these anatomical changes translate to functional differences in descending serotonergic modulation after neonatal adverse experiences.

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. Sprouting of descending serotonergic axons, originating from the rostroventral medulla, as well as changes in receptor function and expression take place in the first postnatal weeks of rodents, corresponding to human neonates in early infancy. Descending serotonergic modulation switches from facilitation in early life to bimodal control in adulthood, masking an already functional 5-HT inhibitory system at early ages. Specifically the 5-HT3 and 5-HT7 receptors seem distinctly important for pain facilitation at neonatal and early infancy, while the 5-HT1a, 5-HT1b, and 5-HT2 receptors mediate inhibitory effects at all ages. Analgesic therapy that considers the neurodevelopmental phase is likely to result in a more targeted treatment of neonatal pain and may improve both short- and long-term effects. IMPACT: The descending serotonergic system undergoes anatomical changes from birth to early infancy, as its sprouts and descending projections increase and the dorsal horn innervation pattern changes. Descending serotonergic modulation from the rostral ventral medulla switches from facilitation in early life via the 5-HT3 and 5-HT7 receptors to bimodal control in adulthood. A functional inhibitory serotonergic system mainly via 5-HT1a, 5-HT1b, and 5-HT2a receptors at the spinal level exists already at the neonatal phase but is masked by descending facilitation.

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. Sprague-Dawley rat pups received four unilateral needle pricks per day, while controls received four tactile stimuli or were left completely undisturbed during the first postnatal week. Mechanical sensitivity was assessed in the neonatal phase and throughout the development. State anxiety was assessed in the open field test and trait anxiety in the elevated zero maze. The results show that repetitive needle pricking leads to acute mechanical hypersensitivity, but does not affect baseline mechanical sensitivity throughout development. In adulthood, animals previously exposed to neonatal procedural pain (including repetitive handling and removal from litter) showed lower state anxiety but did not differ in trait anxiety, as compared with the undisturbed controls. These findings indicate that early-life procedural pain decreases state but not trait anxiety behavior in later life in a rodent model of repetitive needle pricking.

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. Paramount in order to estimate the clinical usefulness of a radiological imaging is to establish the reproducibility of the radiological scoring system. A reproducible and clinically feasible diagnostic scoring system was developed to estimate cervical degeneration on standard cervical X-rays. MATERIALS AND METHODS: A reproducibility study for the interpretation of degenerative abnormalities on standard cervical X-rays was performed, using a dichotomous outcome (degenerative abnormalities present Yes/No). The estimation of intervertebral disc height loss on standard cervical X-rays was validated with computed tomography (CT) scan measurements. RESULTS: Five radiological degenerative features on standard cervical X-rays (disc height loss, anterior vertebral osteophytes, posterior vertebral osteophytes, vertebral end plate sclerosis, and uncovertebral osteoarthritis) showed a substantial to excellent reproducibility (kappa value ≥ 0.60). The qualitative definition of disc height loss used in the reproducibility study showed a substantial agreement with the actual measurements of disc height loss on CT scan (kappa value = 0.69). CONCLUSION: Subjective judgment of a cervical standard X-ray is a reproducible method to demonstrate degenerative abnormalities of the cervical spine.

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. There are no randomized controlled trials on RF denervation in patients with chronic cervical facet joint pain. METHODS: Patients were randomized to receive RF denervation combined with bupivacaine (intervention group) or bupivacaine alone (control group). In the intervention group, an RF thermal lesion was made at the cervical medial branches after the injection of bupivacaine. The primary outcome was measured at 6 months and consisted of pain intensity, self-reported treatment effect, improvement on the Neck Disability Index, and the use of pain medication. Duration of effect was determined using telephone interviews. RESULTS: We included 76 patients. In the intervention group, 55.6% showed > 30% pain decrease versus 51.3% in the control group (P = 0.711); 50.0% reported success on the Patients' Global Impression of Change in the intervention group versus 41.0% (P = 0.435); the Neck Disability Index was 15.0 ±â€Š8.7 in the intervention group compared with 16.5 ±â€Š7.2 (P = 0.432), the need for pain medication did not differ significantly between groups (P = 0.461). The median time to end of treatment success for patients in the RF group was 42 months, compared with 12 months in the bupivacaine group (P = 0.014). CONCLUSIONS: We did not observe significant differences between RF denervation combined with injection of local anesthesia compared with local anesthesia only at 6 months follow-up. We found a difference in the long-term effect after 6 months follow-up in favor of the RF treatment.Level of Evidence: 2.

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. METHODS: Sprague-Dawley rat pups received either methadone (1 mg/kg) or saline prior to repetitive needle pricks into the left hind paw from the day of birth (postnatal day (P)0) to P7. Control littermates received a tactile stimulus. Mechanical sensitivity was assessed during the neonatal period (P0-P7), from weaning to adulthood (3-7 weeks) and following surgical re-injury of the same dermatome in adulthood. RESULTS: Methadone administration completely reversed acute hypersensitivity from P0 to P7. In addition, neonatal methadone analgesia prevented prolonged hypersensitivity after re-injury in adulthood, without affecting sensitivity from weaning to adulthood. CONCLUSIONS: The current study shows that neonatal methadone analgesia can attenuate acute as well as long-term hypersensitivity associated with neonatal procedural pain in a rat model. IMPACT: Methadone treatment attenuates acute and long-term hypersensitivity associated with neonatal pain in a rat model. Clinical effectiveness studies are urgently warranted to assess acute and long-term analgesic effectivity of methadone.

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. In this review, a systematic literature search was conducted using three databases: Medline, Embase, and PubMed. A quality assessment was performed on predetermined entities of bias. Thirteen articles were identified to be relevant. The results show that NMDAR subunits and splice variants are dynamically expressed during postnatal development in the spinal dorsal horn. During the first 2 weeks, the expression of less excitable GluN2A subunit and more sensitive GluN2B subunit increases while the expression of high excitable GluN2C subunit decreases. During the 2nd week of postnatal development GluN1 subunits with exon 21 spliced in but exon 22 spliced out are predominantly expressed, increasing phosphorylation, and transport to the membrane. The data suggest that in rats, the nociceptive system is most susceptible to central sensitization processes during the first two postnatal weeks. This may have important consequences for nociception and pain responses in later life. From this, we conclude that targeted therapy directed toward specific NMDAR subunits is a promising candidate for mechanism-based treatment of pain in neonates.

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. Control pups were left undisturbed (n = 17). When adult (6-8 weeks), lumbar wide-dynamic-range neuron activity in laminae III-V was recorded using in vivo extracellular single-unit electrophysiology. Spike activity evoked by cutaneous dynamic tactile (brush), pinch and punctate (von Frey hair) stimulation, and plantar receptive field areas were recorded, at baseline and 2 and 5 days after left plantar hind paw incision. Baseline brush receptive fields, von Frey hair, and pinch sensitivity were significantly enhanced in adult NP and TC animals compared with undisturbed controls, although effects were greatest in NP rats. After incision, injury sensitivity of adult wide-dynamic-range neurons to both noxious and dynamic tactile hypersensitivity was significantly greater in NP animals compared with TC and undisturbed controls. We conclude that both repeated touch and needle-prick stimulation in the neonatal period can alter adult spinal sensory neuron sensitivity to both innocuous and noxious mechanical stimulation. Thus, spinal sensory circuits underlying touch and pain processing are shaped by a range of early-life somatosensory experiences.

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 rats received either four needle pricks per day in the left hind-paw from postnatal day 0-7 as a model of procedural pain in infancy. Control pups were handled in the same way but were instead tactile stimulated, or were left undisturbed. At the age of 8 weeks, all animals received an ipsilateral hind-paw incision as a model for post-operative pain, and mechanical sensitivity was tested at multiple time-points. Before, and 1 or 5 days post-incision, spinal cord tissue was collected for immunostaining of opioid receptor OPRM1. Semi-quantitative immunocytochemical analysis of superficial laminae in lumbar spinal dorsal horn revealed that: (1) early life repetitive tactile or noxious procedures do not alter baseline levels of OPRM1 staining intensity and (2) early life repetitive tactile or noxious procedures lead to a decrease in OPRM1 staining intensity 5 days after incision in adulthood compared to undisturbed controls. We conclude that early life repetitive tactile or noxious procedures affect the intensity of OPRM1-immunoreactivity in the lumbar superficial spinal cord dorsal horn after adulthood injury, without affecting baseline intensity. © 2018 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc. Develop Neurobiol 78: 417-426, 2018.

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. This procedure is performed under fluoroscopic guidance. Currently, three approaches are described and used. Those three techniques of radiofrequency treatment of the CMBs, classified on the base of the needle trajectory toward the anatomical planes, are as follows: the posterolateral technique, the posterior technique, and the lateral technique. We describe the three techniques with their advantages and disadvantages. Anatomical studies providing a topographic anatomy of the course of the CMBs are reviewed. We developed a novel approach based on the observed strengths and weaknesses of the three currently used approaches and based on recent anatomical findings. With this fluoroscopic-guided approach, there is always bone (the facet column) in front of the needle, which makes it safer, and the insertion point is easier to determine without the risk of positioning the radiofrequency needle too dorsally.

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. We assessed the predictors of PRF in patients with chronic intractable lumbosacral radicular pain. METHODS: Patients with monosegmental chronic lumbosacral radicular pain of L5 or S1 first received a selective nerve root block at the corresponding level. Independent of the result of this block a PRF treatment at the same level was performed. At 6 weeks, 3 months, and 6 months after the procedure the outcome was evaluated. RESULTS: A positive diagnostic nerve root block and age ≥ 55 were predictive factors for successful outcome at 6 months, while disability was a negative predictor.The use of failed back surgery syndrome, gender, duration of pain, Numerical Rating Scale, level and side of treatment, DN4, and RAND-36 as predictors for success was not supported. CONCLUSIONS: Successful outcome after PRF adjacent to the DRG, in patients with intractable chronic lumbosacral radicular pain, is more likely in patients ≥ 55 years, with limited disability and after a positive diagnostic nerve root block. A combination of all these factors creates a fair predictive value (AUC: 0.73).

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. The list was also intended to be used as the basis for a set of criteria for registered status of pain treatment facilities. METHODS: The University Pain Center Maastricht at the Department of Anesthesiology and Pain Management of the Maastricht University Medical Center conducted a 3-round Delphi study in collaboration with the Board of the Pain Section of the Dutch Society of Anesthesiologists (NVA). RESULTS: Twenty-five quality indicators were selected as relevant to 2 types of pain treatment facilities, pain clinics and pain centers. The final expert-agreed list consisted of 22 quality indicators covering 7 quality domains: supervision, availability of care, staffing level and patient load, quality policy, multidisciplinarity, regionalization, and research and education. CONCLUSIONS: This set of quality indicators may facilitate organizational evaluation and improve insight into service quality from the perspectives of patients, pain specialists, and other healthcare professionals. Recommendations for improvements to the current set of quality indicators are made. In 2014 the process of registering pain treatment facilities in the Netherlands started; facilities can register as a pain clinic or pain center.

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%. At baseline, a set of risk factors including pain-related variables, psychological factors, and disability was measured. RESULTS: In a multiple logistic regression analysis, higher patient's expectations, neuropathic pain, no severe pain (< 80 mm visual analogue scale [VAS]) were independently related to long-term continuation of TENS. For the outcome "minimally clinical important pain reduction," the multiple logistic regression analysis indicated that no multisited pain (> 2 pain locations) and intermittent pain were positively and independently associated with a minimally clinical important pain reduction of ≥ 33%. CONCLUSION: The results showed that factors associated with a successful outcome in the long term are dependent on definition of successful outcome.

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. METHOD: The University Pain Centre Maastricht in the Department of Anaesthesiology and Pain Management at Maastricht University Medical Centre developed a questionnaire survey based on the Recommendations for Pain Treatment Services of the International Association for the Study of Pain (IASP). The questionnaire was sent to the medical boards of all hospitals in the Netherlands (n=94). RESULTS: The response rate was 86% (n=81). Of all hospitals, 88.9% (n=72) reported the provision of organized specialized pain care, which was provided by a pain management team in 86.1% (n=62) and by an individual specialist in 13.9% (n=10). Insight was obtained from pain treatment facilities in five different domains: the organizational structure of pain management, composition of the pain team, pain team practice, patient characteristics, and research and education facilities. CONCLUSION: Although 88.9% of all hospitals stated that organized specialized pain care was provided, only a few hospitals could adhere to the criteria for pain treatment services of the IASP. The outcome of the questionnaire survey may help to define quality improvement standards for pain treatment facilities.

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. Inflammatory mediators including tumor necrosis factor α are released from the nucleus pulposus and the degenerating peripheral nerve, which, in turn, induces production of neurotrophins like nerve growth factor and brain-derived neurotrophic factor. Neurotrophins interfere not only with the generation of ectopic firing of nociceptive neurons in the dorsal root ganglion but also with the excitability and sensitization of neuronal transmission in the dorsal spinal horn. Radicular pain is further characterized by the electrophysiological spreading of the afferent nociceptive input over different spinal nerve roots. Both the complex pathophysiological pathways involved and the spreading of the nociceptive signal make radicular pain difficult to treat. Pulsed radiofrequency (PRF) is considered an option in treatment of radicular pain. To understand and increase the efficiency of PRF interventional treatments in radicular pain, both in vitro and in vivo studies aiming at elucidating part of the mechanism of action of PRF are described. Potential factors that may improve the efficacy of PRF treatment in radicular pain are discussed.

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). Since the descending pain inhibitory circuit matures perinatally, perinatal SSRI exposure has been shown to affect pain sensitivity in offspring. In the present review, we summarize experimental and clinical evidence for the effect of perinatal maternal stress and SSRI exposure on pain sensitivity in offspring. Both experimental and clinical studies show the effect of perinatal maternal stress on regulation of the hypothalamic-pituitary-adrenal (HPA) system and the serotonin pain inhibitory system. Alterations in these two systems likely underlie long-term alterations in the development of pain sensitivity. This review sheds light on the effect of perinatal maternal stress and treatment with SSRIs on offspring pain sensitivity, in relation to the developing HPA system and 5-HT signaling.

Long-term follow-up of cervical facet medial branch radiofrequency treatment with the single posterior-lateral approach: an exploratory study.

BACKGROUND: Over 50% of patients presenting to pain clinic with neck pain have the cervical facet joints as the source of pain. Radiofrequency (RF) treatment of the medial branch, innervating the facet joint, is a therapeutic option. The objectives of this study were to evaluate the therapeutic effect and its duration of RF treatment, using the single posterior-lateral approach in patients suffering from facet joint degeneration and to identify predictors for a long-term effect. METHODS: Of the 130 consecutive patients with axial neck pain referred to the University Pain Center Maastricht, 67 fulfilled the inclusion criteria. The therapeutic effect was measured using the Patients' Global Impression of Change (PGIC) scale. Retrospective data were made complete using newly collected PGIC follow-up data. A Kaplan-Meier curve evaluated the long-term therapeutic effect. Possible predictors of outcome were evaluated. RESULTS: Two patients refused to participate and in the remaining 65 patients, overall pain relief was reported in 55.4% at 2-month follow-up. Moderately, important change of improvement and substantial change of improvement were seen in 50.8% of patients. At 3-year follow-up, 30% still reported pain reduction. Spinal treatment level was the only predictor found. CONCLUSIONS: Radiofrequency treatment of the cervical facet joints using a single posterior-lateral approach is a promising technique in patients with chronic neck pain due to facet degeneration. The short-term and long-term therapeutic effects of this intervention justify a randomized controlled trial to estimate the efficacy of cervical facet joint RF treatment in a chronic neck pain population.

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. METHODS: An anatomical model of a cervical spine, embedded in gelatin, was inserted in a specially developed measurement device. This provided ultrasound images of cervical bony structures. Anatomical validation was achieved by laser light beams projecting the center of the ultrasound image on the cervical bony structures through a transparent gelatin. RESULTS: Anatomically validated ultrasound images of different cervical bony structures were taken from dorsal, ventral, and lateral perspectives. Potentially relevant anatomical landmarks were defined and validated. Test/retest analysis for positioning showed a reproducibility with an intraclass correlation coefficient for single measures of 0.99. Besides providing validated ultrasound images of bony structures, this model helped to develop a method to detect and count the cervical segmental levels in vivo at long-axis position, in a dorsolateral (paramedian) view at the level of the laminae, starting from the base of the skull and sliding the ultrasound probe caudally. CONCLUSIONS: Ultrasound bony images of the cervical vertebrae were validated with an in vitro model. Anatomical bony landmarks are the mastoid process, the transverse process of C1, the tubercles of C6 and C7, and the cervical laminae. Especially, the cervical dorsal laminae serve best as anatomical bony landmarks to reliably detect the cervical segmental levels in vivo.