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 Table of Contents  
REVIEW ARTICLE
Year : 2020  |  Volume : 34  |  Issue : 3  |  Page : 151-159

Role of ultrasound in chronic pain management


1 Department of Anesthesiology and Pain Management, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India
2 Department of Anesthesia and Pain Medicine, University Health Network.Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada

Date of Submission17-Sep-2020
Date of Decision29-Oct-2020
Date of Acceptance03-Nov-2020
Date of Web Publication28-Dec-2020

Correspondence Address:
Prof. Philip W H. Peng
Department of Anesthesia and Pain Medicine, University Health Network-Toronto Western Hospital, University of Toronto, Toronto, Ontario
Canada
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijpn.ijpn_133_20

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  Abstract 


Ultrasound application in interventional pain medicine has made tremendous growth in recent years. Ultrasound not only avoids radiation exposure but also allows real-time visualization of the drug delivery and avoids damage to the surrounding structures. It also ensures accurate delivery of medication; thus improves efficacy and outcome. Furthermore, ultrasound is a valuable tool for pain physicians in confirming the diagnosis of many musculoskeletal pain conditions and entrapment neuropathies in the clinic. Its role in various aspects of chronic pain like spinal pain, musculoskeletal pain and nerve-related pain are discussed below.

Keywords: Chronic pain, musculoskeletal, nerves, ultrasound


How to cite this article:
Sahoo RK, H. Peng PW. Role of ultrasound in chronic pain management. Indian J Pain 2020;34:151-9

How to cite this URL:
Sahoo RK, H. Peng PW. Role of ultrasound in chronic pain management. Indian J Pain [serial online] 2020 [cited 2021 Apr 13];34:151-9. Available from: https://www.indianjpain.org/text.asp?2020/34/3/151/305138




  Introduction Top


Application of ultrasound in pain medicine (USPM) has grown rapidly in the past two decades, as evidenced by the astonishing surge of publications in the literature, and the remarkable increase in USPM courses held by various organizations. The first objective of this article is to describe how the application of ultrasound evolves in pain management. The second objective is to discuss the expanding role of ultrasound in pain interventions.


  Application of Ultrasound in Pain Intervention Top


Ultrasound allows visualization of soft tissues (nerves, muscles, tendons, ligaments, vessels, and fascia planes) and bone surface. Thus, it enhances the accuracy, reliability (precision), and safety of the procedure.[1],[2] Real-time application enables dynamic assessment of a structure (e.g., tracing a nerve) or tissue movement (e.g., supraspinatus impingement) and visualization of needle advancement or medication administration in interventions. The equipment itself is affordable, portable, and free of radiation hazard to the provider and the patient. A comparison between ultrasound, fluoroscopy, and computed tomography is summarized in [Table 1]. However, the quality of ultrasound scan is operator dependent and the use of ultrasonic wave is hampered when the target tissue is deep or obstructed by the bone surface. Low-frequency probe is generally used to visualize the deeper tissue, but the resolution will deteriorate with depth. Bone has a high attenuation coefficient and structures deep to the bone cannot be seen. These are the limitations of applying ultrasound in pain interventions.
Table 1: Advantages and disadvantages of various imaging modality used for interventional pain management

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Most of the earlier literature on USPM was mainly on the development of new procedures and validation of the accuracy of the procedures. In recent years, more publications are comparing ultrasound with other modalities, mainly fluoroscopy, in their efficacy, and more outcome studies are published. Furthermore, ultrasound facilitates applications to a lot of new procedures in the areas of peripheral nerves, musculoskeletal (MSK) structures, and spine targets. This will be discussed below in three broad headings.


  Nerve Management Top


Ultrasound ensures accuracy and safety of the procedure

Ultrasound provides direct visualization and dynamic scanning of the nerves and the surrounding structures and real-time appreciation of the spread of medication. This capability enables identification of the potential site of entrapment while the recognition of surrounding structures such as vessels or vital organs minimizes the risk of inadvertent injuries.

Before the emergence of ultrasound, peripheral nerve blocks were mostly performed with landmark guidance. Literature suggested a significant improvement in the accuracy with the use of ultrasound as exemplified by the blockade of lateral femoral cutaneous nerve (LFCN).

The course of LFCN is notoriously variable.[3] Accuracy of landmark-guided technique ranged between 5% and 40%.[4],[5] With ultrasound guidance, the early experience suggested a success rate between 80% and 100%.[2],[6] However, the anatomic variation and the size can pose a challenge in locating the nerve with ultrasound. The ultrasound technique was recently refined by Nielsen et al. and they advocated to seek for the nerve initially at the “fat-filled groove” between the tensor fascia lata and sartorius 10 cm or four-finger breadth distal to anterior superior iliac spine [Figure 1].[7] Subsequently, the nerve can be traced cephalad close to the entrapment site for carrying out the intervention. With this method, they were able to accurately inject dye around the LFCN in cadaver and anesthetize the nerve in volunteers with an accuracy of 100% and 95%, respectively. This increase in accuracy also translates to an increase in the outcome of treatment.[8]
Figure 1: The fat-fill groove between sartorius (SAR) and tensor fascia lata. Within this groove, the lateral femoral cutaneous nerve can be easily identified. The left diagram showed the position of the ultrasound probe which is four-finger breadth distal to the anterior superior iliac spine. Reprinted with permission from Philip Peng Educational Series

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In addition to the increase in accuracy, ultrasound promotes the safety of the procedure. One good example is the performance of stellate ganglion block. Although the stellate ganglion is located at C7-T1 level, the conventional target is at C6 or C7 and the technique relies on the deposition of the local anesthetic to the cervical sympathetic trunk (CST) in the prevertebral fascia [Figure 2].[2] In the past, this procedure used to be performed with landmark or with fluoroscopy guidance. Since the CST is defined by the fascial plane, ultrasound, not fluoroscopy, is the imaging technique of preference. In addition, the target is surrounded by many important vessels such as vertebral, inferior thyroidal, and ascending cervical arteries; hence, it will be prudent to have an ultrasound to locate and avoid the vessels rather than the detection of the intravascular puncture with fluoroscopy and contrast injection after the needle puncture to the vessel [Figure 3].[9],[10] In addition, the paratracheal trajectory of the needle path in conventional technique puts the esophagus at risk [Figure 3].[10] A lateral-to-medial in-plane under ultrasound guidance approach is a safer needle injection trajectory [Figure 4].[11]
Figure 2: The figure showed the sixth cervical vertebra (*) and the anterior tubercle (A). This is the landmark for the conventional approach. However, the target, cervical sympathetic chain between the middle cervical sympathetic and stellate ganglion is defined by the fascial plane. Reprinted with permission from Philip Peng Educational Series

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Figure 3: Top left, right figures and lower left figure showed different aberrant vessels (bold arrows) at the level of C6. Lower two figures showed the presence of esophagus (E) outlined by arrowheads. Reprinted with permission from Philip Peng Educational Series

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Figure 4: Figure showing the medial (out-of-plane) approach or lateral in-plane approach. The target is the prevertebral fascia (arrows). SCM: Sternocleidomastoid muscle, LCa: Longus capitis muscle, LC: Longus colli muscle, AT: Anterior tubercle, T: Trachea, N-C6 nerve root, **internal jugular vein, solid line: Medial out-of-plane approach: Dotted line: Lateral in-plane approach. Reprinted with permission from Philip Peng Educational Series

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Diagnosis of nerve entrapment

Modern ultrasound allows accurate identification of peripheral nerve entrapment. The very early sonographic sign of nerve entrapment includes decreased echogenicity, flattening at the entrapment site and later, enlargement of the nerve proximal to the site of the entrapment. Another important clinical sign is the reproduction of typical neuropathic pain features along the nerve distribution which can occur with transducer pressure over the entrapment site (Sono-Tinel sign). It is important to be well aware of the functional anatomy where the nerves can potentially get entrapped as they pass through an osteofibrous tunnel or intermuscular plane to allow a proper probe placement and dynamic assessment.[12],[13]

Common entrapment neuropathies in the upper extremity include the median nerve at the carpal tunnel and ulnar nerve at the cubital tunnel. Ultrasound has been described in the diagnosis and quantification of the severity of nerve entrapment in carpal tunnel syndrome (CTS),[14] which is mainly a clinical diagnosis based on history and characteristic signs [Figure 5].[15] In atypical cases, electrophysiological studies aid in confirming the diagnosis. In recent times, ultrasound has provided new dimensions to the diagnosis of CTS by measuring the cross-sectional area (CSA) of the nerve, vascularity, morphological change (flattening), and the possible etiology such as cysts, ganglion, or tendinopathy [Figure 6].[16] Usually, the CSA of a normal median nerve measures <8 mm2 at the level of the volar wrist crease and is considered abnormal when >12 mm2.[17] Literature suggests that the degree of median nerve enlargement directly correlates with the severity of CTS, with a threshold of 12.8 mm2 and 14 mm2 considered as moderate and severe CTS, respectively.[18] Using the CSA at the level of the proximal pronator quadratus as control, a 2 mm2 or greater difference in CSA between the maximal enlargement (at carpal tunnel level) and the control supports the diagnosis of CTS with 99% sensitivity and 100% specificity using electrophysiological test as a standard of reference.[14] In addition, increased power Doppler imaging within the median nerve can indicate CTS with 95% accuracy and correlate with severity of the CTS.[19]
Figure 5: Carpal tunnel. Please note the recurrent branch and palmar cutaneous branch of median nerve. Reprinted with permission from Philip Peng Educational Series

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Figure 6: Short-axis view of the carpal tunnel (proximal) shows the honeycomb appearance of normal median nerve (M) with multiple rounded hypoechoic fascicles surrounded by hyperechoic perineurium and epineurium. UA: Ulnar artery, arrowheads: flexor retinaculum (hypoechoic), M: median nerve, FCR: Flexor carpi radialis, FPL: Flexor pollicis longus, *-ulnar nerve; FDS: Flexor digitorum superficialis, FDP: Flexor digitorum profundus. Reprinted with permission from Philip Peng Educational Series

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Electrophysiological test is a useful diagnostic modality in entrapment neuropathies and the use of ultrasound can complement each other. In cubital tunnel syndrome at the elbow, the addition of sonography to electrodiagnostic tests not only increases sensitivity from 78% to 98% but also helps in localizing the lesions which otherwise was not possible to identify with electrodiagnostic tests alone.[20],[21]

Allow safe use of intraneural or perineural chemical ablation

Back in 1920, Lewis had published the use of intraneural administration of 60% alcohol directly into major nerves (sciatic, median, or ulna) through surgical exposure for the treatment of causalgia. This procedure controlled the pain successfully and did not result in neuropathic pain.[22] Unfortunately, the experience chemical ablation of nerve in the subsequent years was poor and resulted in even worsening of neuropathic pain.[23] Two factors were hypothesized contributing to these adverse outcomes: (1) partial neurolysis resulted in irritation of nerve leading to subsequent neuropathic pain and (2) spilling of neurolytic agent to surrounding structures caused local damage and irritation leading to soft-tissue pain.

With the increasing use of ultrasound, there is a resurgence of interest in performing chemical ablation of the nerve. Ultrasound provides clear image of the nerve or neuroma [Figure 7], allowing a precise intraneural administration of a small amount of neurolytic agent in neuroma without the risk of spreading to the surrounding innocent structures.[24],[25] In situations where a network of fine nerves such as articular branches to a joint can be targeted for neural ablation, ultrasound allows the visualization of a fascia plane where the neurolytic agent can be contained within a soft-tissue plane. This had been examined in the hip and knee articular branches.[26],[27] In all those reports, the presence of neuropathic pain was absent suggesting the safety of the well-executed intraneural or perineural chemical ablation.
Figure 7: The left panel showed the Morton's neuroma between the third and fourth metatarsal. A corresponding sonography is showed on the right and the yellow arrow indicated the neuroma. Reprinted with permission from Philip Peng Educational Series

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Peripheral nerve stimulator insertion

The concept of peripheral nerve stimulation was introduced in the late 1960s but did not gain popularity because the surgical approach was the only access to the exposure of peripheral nerve and there was no dedicated stimulator system available for the peripheral nerve stimulation.[28] As a result, the implanted systems were prone to migration, lead fracture, erosion, and infection, leading to unpredictability of the outcomes.[28] In the past two decades, there is a resurgence of this technique due to two major developments. One is the development of the dedicated system with a specialized lead that anchors the nerve coupled with an externalized implantable pulse generator. Another advance is related to the use of ultrasound that allows the insertion of the system percutaneously without resorting to surgical incision.[29] The latter is important in the evolution of the peripheral nerve stimulator as it enables a noninvasive percutaneous trial and extends the procedure practice to nonsurgical personnel such as anesthesiologists.

The renew of interest for peripheral nerve stimulation started in 1999 when Weiner et al. published a report on implanting percutaneous leads, originally designed for spinal cord stimulation, to stimulate occipital nerve for treatment of occipital neuralgia.[30] Since then, the peripheral nerve stimulation had been applied to neural targets for headache and facial pain, neuropathies of upper extremities, neuralgia- or neuroma-related pain of lower limbs, and neuropathic pain of abdominopelvic wall.[31]

Nerve decompression

Ultrasound plays an important role in diagnosing entrapment neuropathy.[32] In addition, ultrasound provides an opportunity for minimally invasive decompression procedure, which is currently achieved by the surgical approach. Management of CTS exemplifies these two advantages from the ultrasound.

Carpal tunnel release can also be achieved with ultrasound-guided percutaneous decompression. The most common method is the use of a hook blade.[33] The flexor retinaculum comprises two layers: superficial and deep layers.[34] The superficial layer is continuous with the antebrachial fascia and the complete release of the nerve is made possible by transection of the deep fiber only. The experience with this procedure is very safe.[16],[33] By minimizing the incision and thus the scar, the recovery is shorter than that from open surgery. Other ultrasound-guided techniques have also been described with a thread-based transection system[35] or by needle fenestration.[36]

Hydrodissection

One of the nonsurgical options for nerve release is ultrasound-guided hydrodissection of the perineural fibrous and scar tissue.[13] This is a nonsurgical adhesiolysis achieved by introducing fluid under pressure into the plane of dissection [Figure 8].[37] The rationale behind the hydrodissection is to relieve the pressure of the neurovascular structures on the epineurium: nervi nervorum and vasa nervorum.[38] Adhesion or compression on a peripheral nerve can cause venous congestion and impair lymphatic drainage, thus jeopardizing the homeostatic regulation of the endoneural microenvironment. Hydrodissection potentially alleviates the congestion and free the nervi nervorum from the surrounding soft tissue.
Figure 8: Top left: The superficial branch of radial nerve (arrow) in the subcutaneous plane superficial to the radius. Top right: A needle (arrowheads) is inserted deep to the nerve. Lower left: Using dextrose solution (yellow), the nerve is separated from the periosteum of the radius. Lower right: Insertion of the needle superficial to the nerve and with further hydrodissection of the nerve with dextrose solution, the nerve is now free from adhesion from the surrounding tissue. Reprinted with permission from Philip Peng Educational Series

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A recent randomized controlled trial comparing hydrodissection with 5 ml normal saline inside the carpal tunnel with the same amount of normal saline deposit superficial to the retinaculum (control) supported the clinical effectiveness of hydrodissection of median nerve within the carpal tunnel with normal saline. Using a validated questionnaire to assess the severity and functional status, hydrodissection resulted in improvement in pain and function even at 6 months after the treatment.[39] Dextrose 5% is more commonly used for hydrodissection and there is some evidence to suggest that it is superior to normal saline and steroid for hydrodissection.[40],[41]


  Musculoskeletal Pain Management Top


Ultrasound helps in diagnosis of musculoskeletal pain conditions

Ultrasound often complements the bedside clinical examination in many MSK pain conditions such as lateral epicondylitis, tendinopathies, tenosynovitis, and tendon tears. Rotator cuff (RC) disorders constitute a common cause of chronic shoulder pain and disability. Conventionally, magnetic resonance imaging (MRI) had been used as a diagnostic imaging modality of choice to identify various RC pathologies. However, ultrasound is gaining popularity for its reliable point of care dynamic assessment. A systematic review compared the diagnostic accuracy of ultrasound, MRI, and magnetic resonance arthrography (MRA) in various RC disorders revealed that all three modalities provided comparable high sensitivities and specificities (over 0.90) in the diagnosis of full-thickness RC tears. In diagnosing partial RC tears, the specificities of all three modalities are also comparably high (0.93–0.94), but the sensitivity is higher in MRA (0.83) compared with ultrasound and MRI (0.68 and 0.67, respectively).[42]

Improved accuracy, safety, and outcome of musculoskeletal interventions

Ultrasound is commonly used for the intra-articular (IA) injections of various large joints such as the hip, knee, ankle, and shoulder. The injectates include corticosteroids, viscosupplement, prolotherapy, and platelet-rich plasma. For the therapeutics to be effective, accurate needle placement is imperative. Various studies have demonstrated that US improves accurate needle placement and thus improves outcome, safety, and cost-effectiveness.

Knee joint injection is commonly performed by rheumatologists and orthopedic surgeons using landmark-guided technique, although the literature suggested an accuracy of 79% (40%–100%).[43] More practitioners are performing knee IA injection with ultrasound guidance.[44] In a comprehensive review comparing the accuracy of ultrasound and landmark-guided knee injection, the accuracy of various landmark-guided knee IA injections was estimated to be 78% compared with 97% with ultrasound guidance.[45] One of the major reasons for the failure of landmark-guided injection is the placement of needle in the fat pad inside the knee, which also provides loss-of-resistance feeling, a false sense of IA placement of needle [Figure 9] and [Figure 10].[46] Furthermore, patients in the ultrasound group reported less postprocedural pain and better pain relief and function compared with landmark-based techniques.[47] Accurate placement of needle translates to better outcome. In an outcome study involving a large number of patients with knee osteoarthritis who received viscosupplement under ultrasound or landmark-guided technique (500 ultrasound guided and 647 landmark guided), significantly fewer patients in the ultrasound cohort went to surgery compared to the landmark-guided cohort (33.2% and 45.8%, respectively; P < 0.001). In addition, subgroup analysis for patients with high body mass index showed even larger differences (34.8% vs. 51.8%; P < 0.001). The authors concluded that ultrasound guidance improves the accurate delivery of medication and better pain relief and outcome.[48]
Figure 9: Sonography of the suprapatellar view of the normal knee. The insert showed the position of the patient and the ultrasound probe. SPFP: Suprapatellar fat pad, PFFP: Prefemoral fat pad, P: Patella, F: Femur; ** indicates the suprapatellar recess. Note the trilaminar structure of quadricep tendon. Reproduced with permission from Philip Peng Educational Series

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Figure 10: Figure showed the injection technique. The ultrasound probe is placed between the patella and quadriceps tendon initially and then turn 90° upon visualization of the suprapatellar recess. The needle is then approach from lateral to medial to avoid puncturing the quadriceps tendon. The needle is indicated by the arrowheads and the suprapatellar recess by asterisks (****). R: Retinaculum, Q: Quadriceps tendon, F: Femur. Reproduced with permission from Philip Peng Educational Series

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Similarly, better accuracy, efficacy, and outcomes have been reported in ultrasound-guided hip and shoulder injections compared to landmark-based technique.[1],[49]

Enable specific ultrasound-guided procedures

Most of the injection techniques described in pain related to the MSK system are administered either directly into the joint or around the structures such as tendon or ligament. However, the success of some procedures requires the precise placement of needle inside the structures and ultrasound allows those procedures to be performed safely and precisely.[50] Two examples will be discussed below.

Peritendinous injection is considered when the injectate reaches the pathologic site of the tendon such as tenosynovitis or bursal tear of the tendon. However, it becomes an issue in the situation of tendinopathy.[51] Fenestration with or without administrating agents for regeneration such as platelet-rich plasma will be required for the treatment for tendinosis [Figure 11]. The procedure required precise visualization of the targeted tendon and strategical placement of the needle in different parts of the diseased tendon under ultrasound guidance.[52]
Figure 11: Upper figure showed the common extensor tendon origin (arrows) with tendinosis (*), which is evident with mixture of hypoechoic and hyperechoic signal. Lower figure showed the needle inserted into the common extensor tendon repeatedly in different parts of common extensor tendon. R: Radial head, C: Capitellum, LE: Lateral epicondyle. Reproduced with permission from Philip Peng Educational Series

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Calcific tendinitis is a condition due to the deposition of calcium crystals. Three distinct stages have been described depending on the disease process and most of the calcific tendinitis occurs in the RC of the shoulder.[53] During the painful stage, the calcium deposit can be fenestrated precisely and removed with the barbotage technique.[54] Extreme care is required not to shatter the shell of the deposit which can result in spillage of calcium into the bursal space. The fenestration and barbotage can be achieved with one- or two-needle system [Figure 12].[55] This procedure can only be achieved with ultrasound guidance.
Figure 12: (a) Needle inser tion into the center of calcium with in-plane method. (b) Fenestration with backward and forward movement. (c) Fenestration with rotation. (d) Fenestration out-of-plane. (e) Fenestration with two needles. (f) Subacromial bursa injection of steroid. Reprinted with permission from Philip Peng Educational Series

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  Role of Ultrasound in Spine Interventions Top


Spine interventions are traditionally performed under fluoroscopy. There is increasing interest in applying ultrasound in spine interventions, but this application is limited by the poor visualization of deep tissue and the marked attenuation of ultrasound beam when crossing the bone. This is reflected in the application of ultrasound in the medial branch block (MBB) in the lumbar and cervical spine.

Application of ultrasound for lumbar facet MBB was developed and validated with high accuracy (90%) in two cadaveric studies by Greher et al.[56],[57] A clinical study examining the accuracy of the ultrasound-guided MBB showed an accuracy of 95%.[58] However, this is important to note that the body mass index of those subjects was all below 25. When applying ultrasound technique to subjects with mean body mass index of 39 (range: 32–54), the success rate was only 62%.[59] This reflects the major limitation of applying ultrasound in deep structures. In addition, the needle trajectory in ultrasound-guided method is not applicable for the performance of radiofrequency ablation.

In contrast, the targets for the cervical medial branches and third occipital nerve are relatively superficial and can be visualized by a linear ultrasound probe.[60],[61] These target nerves are possibly be seen in the ultrasound scan,[62] and the trajectory of the needle even allows the feasibility of placement of radiofrequency needle.[63]

In general, there are two ultrasound-guided approaches to the cervical facet articular branches: one is to scan the cervical facet with ultrasound probe placed in the long axis to the cervical spine and placing the needle out-of-plane to the target[62] and another one is to place the probe in short axis to the spine and place the needle in-plane from posterior to anterior to the target (biplanar approach), as shown in [Figure 13] and [Figure 14].[64] The success rates of the later procedure are high – 95%, 100%, 97.5%, and 96% in the third occipital nerve, C5, C6, and C7 MBB, respectively.[61],[64],[65] The randomized control trials comparing with fluoroscopy showed that the ultrasound technique was associated with a lower rate of vascular puncture and shorter performance time.[64],[65],[66] The former is perceivable as ultrasound can visualize the vasculature.[67],[68] Overall, the ultrasound technique allows an alternative to fluoroscopy technique with high accuracy, shorter performance time, and lower vascular puncture rate.[69]
Figure 13: Coronal scan of the cervical spine demonstrating the articular pillars of C3, C4, C5, as well as the inferior articular process of C2. In the long axis, the articular pillars appear as a series of peaks (zygapophyseal joints lines) and valleys (convex shapes of the articular pillars). This view is used for level and needle position confirmation. The medial branches (mb) of C3, C4, and C5 can be seen, as well as the third occipital nerve. Reprinted with permission from Dr. Rod Finalyson and Philip Peng Educational Series

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Figure 14: Transverse scan of the cervical spine at the level of C6 for needle placement. The centroid of the articular pillar forms a distinct flat hyperechoic line and constitutes the target for cervical medial branch blocks. The semispinalis capitis muscle inserts on the posterior tubercle of the transverse process and courses over the AP. Further anterior, nerve root and anterior tubercle can be seen. A computed tomography overlay of the same bony landmarks is depicted in the right lower inset. When performing a cervical medial branch block, the injectate should be deposited along the periosteum of the articular pillar, beneath the SSC. Reprinted with permission from Dr. Rod Finalyson and Philip Peng Educational Series

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  Conclusion Top


In summary, the application of ultrasound to interventional pain procedures offers multiple advantages, including avoidance of radiation risk to providers and patients, easy access for use, and allows real-time assessment and imaging of the region of interest. Since ultrasound provides excellent visualization of the target tissue, the accuracy of the procedure improves which translates to better outcome. The emerging use of ultrasound also opens the opportunities for innovative procedures such as hydrodissection, fenestration, barbotage, and nonsurgical decompression of nerve entrapment.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Nerve Management
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