Peripheral nerve pain overview

Peripheral nerve pain is a common complaint among patients in the clinical setting estimated to affect 7% to 10% of patients above 50 years of age. This condition is a result of damage to the nerves outside of the brain and spinal cord and has a variety of causes from direct damage created by trauma, cancer, and entrapment to more insidious damage from diseases such as diabetes, kidney disease, and infections, with multiple processes frequently co-occurring. Peripheral nerve pain generally consists of one or more symptoms of burning, stabbing, or shooting pain in affected areas. These symptoms often precede or occur simultaneously with motor and sensory deficits depending on the degree of damage and composition of nerve fibers in the affected nerves.

Treatment of neuropathic pain begins with pharmacotherapy usually consisting of one or more drug classes including antidepressants, anticonvulsants, membrane-stabilizing agents and muscle relaxants, local anesthetic patches, nonsteroidal antiinflammatory agents, and, in some cases, opioids. Despite these therapies, patients often receive incomplete pain relief that carries a difficult side effect profile, which can prevent significant improvement in overall quality of life. Beyond pharmacotherapy, peripheral nerve pain is particularly amenable to direct nerve block with local anesthetic and steroids that can directly inhibit pain signal transmission. The advantage of administering considerably less drug comes at the cost of potential mechanical injury and short duration of therapy, thus requiring frequent injections. A subset of patients who experience relief from direct blockage of a nerve transmission by local anesthetics can be candidates for neurolysis depending on the target nerve and clinical scenario. There are multiple methods to accomplish this, all of which extend the pain relief provided with a nerve block at the risk of more severe side effects. There currently are no consensus indications for neurolysis, so the decision to perform neurolysis is made on a case-by-case basis in a step-wise fashion under the supervision of an appropriate clinician that starts with conservative therapy followed by nerve block leading up to neurolysis. Though the treatments are presented in a step-wise fashion, the most effective therapy relies on integration of all available treatments into a multimodal scheme tailored to the patient’s specific needs.

Radiofrequency ablation and pulsed frequency ablation

The underlying principle of ablation relies on deliberate injury of the target nerve resulting in Wallerian degeneration of nerve fibers (i.e., the destruction of nerve axons distal to the lesion) with the goal of interrupting nerve transmission of pain. There are a variety of methods of ablation via chemical (e.g., ethanol, phenol), temperature, and surgery; however, the most common method used in modern pain practice is radiofrequency ablation (RFA).

The earliest method of RFA was “continuous radiofrequency lesioning,” which consisted of the continuous application of radiofrequency electric signals on neural tissue via an electrode attached to a power source providing 0.1 to 1 MHz frequency with the objective of raising the temperature of the targeted tissue above 45 to 50°C for 20 s or more. ^, This temperature and time are considered the “lethal temperature range,” as cell structures exposed to these conditions are known to be destroyed by heat, however, no standard settings have ever been developed. Notably, the radiofrequency probe itself is not the source of heat, but instead the heat is generated by adjacent molecules set into motion by the alternating electromagnetic current, which is then transmitted farther by tissue conductivity ( Fig. 13.1 ). Lesions created by a monopolar RFA needle form an oval around the needle in three-dimensional space that has a measured length (L), width (W), and depth (D) ( Figs. 13.2 and 13.3 ). Factors that influence lesion size are tip diameter (d), tip length (l), tip temperature (T), and lesion time (t) with an increase in any of these variables leading to a larger lesion size.

Diagram revealing the electromagnetically induced movement of molecules surrounding the catheter tip and the relationship between temperature and distance.

(From: Hong K, Georgiades C. Radiofrequency ablation: Mechanism of action and devices. J Vasc Interv Radiol . 2010;21(8 Suppl):S179–186.)

Monopolar lesions are oval. Lesions are measured via length (L) measured in the active tip’s longitudinal direction, lesion width (W) and depth (D) in the tip’s radial direction.

(From: Hong K, Georgiades C. Radiofrequency ablation: Mechanism of action and devices. J Vasc Interv Radiol . 2010;21(8 Suppl):S179–186.)

Progression of the radiofrequency ablation shown by color representation of thermal changes.

(From: Hong K, Georgiades C. Radiofrequency ablation: Mechanism of action and devices. J Vasc Interv Radiol . 2010;21(8 Suppl):S179–186.)

Eventually, the observation that radiofrequency lesioning of the dorsal root ganglion only causes transient sensory loss in the relevant dermatome, but prolonged duration of pain relief prompted the development of a more minimally neurodestructive mechanism of delivering electric current to nerves. ^, This new RFA method termed “pulsed radiofrequency ablation” relies on short pulses (1 to 8 Hz) of high-voltage radiofrequency impulses (500 kHz) applied directly to nerves with the temperature controlled not to exceed 42°C. This new method shown to have significant effect on neurons in animal models has been successfully used for the treatment of myriad pain conditions. ^, The exact mechanism of action is unknown but current research suggests that there is alteration in synaptic transmission resulting in neuromodulation that targets small diameter C and A delta nociceptive fibers.

When comparing the continuous versus pulsed radiofrequency ablation, in general pulsed RFA is considered to provide reduced duration of effect compared to continuous RFA but significantly reduced risk of neural complications. For that reason, for nerves that are purely sensory, continuous RFA is thought to provide improved pain relief for a longer time period. Both RFA and PRF are successfully used in treating peripheral neuralgias. Clinicians need to weigh the risks and benefits when deciding on using RFA versus PRF in peripheral nerves, depending on each individual nerve, type of fibers in the nerve, and nerve function. It is important to remember that RFA will cause nonselective damage to the nerve while PRF provides neuromodulation.

Treatment algorithm

Proper evaluation is key when selecting the appropriate patient for RFA. Evaluation consists of obtaining a thorough history, physical exam, diagnostic laboratory workup, and a recent radiologic evaluation to assess the cause of the pain and to potentially avoid complications from a neurolytic technique. Integration of the patient’s pain with knowledge of the anatomical distribution of nerves may together provide a target nerve that is amenable for treatment. Once a target nerve is identified, the therapeutic potential of nerve ablation begins with a diagnostic nerve block of the target nerve with steroids and local anesthetic with the degree of therapy determining the potential efficacy of denervation.

Nerve selection for ablation has additional concerns to account for compared to a straightforward nerve block with steroids and/or local anesthetic. First and foremost is understanding the makeup of the target nerve, particularly the sensory and motor functions. Performing ablation on a predominantly sensory nerve, has relatively little side effects compared to ablating a nerve responsible for motor function. This concern must be weighed against the degree of potential for therapy in any given clinical scenario, many of which can call for ablation of a major motor nerve such as that encountered with certain types of cancer pain or phantom limb pain. Finally, even when the correct nerve is targeted and there is clear therapeutic benefit, there is an additional need to be as minimally invasive as possible and approach the nerve as proximal to the pain locus to reduce the amount of collateral damage and side effects. Managing these concerns simultaneously is key when deciding when and how to perform an ablation.

Contraindications

Absolute contraindications to neurolysis are patient refusal, active infection at the site of injection, and allergy to the chemical or neurolytic agents. Bleeding is a major concern so special attention needs to be paid to anticoagulation treatment and the presence of bleeding disorders that may contraindicate therapy, especially if injection occurs at a noncompressible site. The presence of a pacemaker is a special case in which proceduralists should consult pacemaker interrogation services.

Complications

Bleeding, infection, pain, and damage to surrounding tissue may occur. Motor nerve denervation may lead to paralysis which in some cases can cause bowel, bladder, or sexual dysfunction. Sensory nerve denervation may lead unintentionally to numbness, and autonomic nerve denervation may lead to hypotension and temperature dysregulation. Occasionally neuritis may develop after partial denervation with a neurolytic agent with subsequent nerve regeneration and hyperesthesia worse than the original pain.

Brachial plexus

General: The brachial plexus is responsible for nearly all of the motor and sensory function of the upper extremities and is therefore considered for RFA in only the most extreme circumstances. One such circumstance is neoplastic brachial plexopathy—a known, rare, late-stage complication of cancer that can occur as a manifestation of neoplasm (frequently breast and lung) or radiation. ^, Due to this, RFA of the brachial plexus has been used in the past for pain originating in the brachial plexus not amenable to conservative management. ^, The brachial plexus can be approached via multiple sites pioneered primarily for the goal of surgical anesthesia. Due to the nonselective damage RFA causes to the nerve, weakness is an expected complication that can be acceptable if patients already have paralysis in their arm or similar neuropathic pathology. Otherwise, PRF will be the preferred method with less but still significant potential for similar complications.

Nerve Anatomy:

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  Nerve roots ( Fig. 13.4 )

  
  
  
  
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    Originates from cervical roots 5, 6, 7, 8, and thoracic root 1

  
  

  
  

  
  

  

  
  

  
  

  Image demonstrating the anatomy of the proximal brachial plexus. Nerves arise from the C5–T1 nerve roots and course distally dividing and combining to form terminal nerves. There are generally five sections (nerve roots, trunks, divisions, cords, branches) before final formation of the nerves of the arm. Notably there is additional division between supraclavicular and infraclavicular branches which are detailed.

  
  

  ((courtesy Netter Atlas of Human Anatomy 2006). From: Netter FH. Atlas of Human Anatomy . Philadelphia, PA: Saunders/Elsevier, 2006. Image 29515.)

  
  
  
  
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  Nerve pathway ( Figs. 13.4 and 13.5 )

  
  
  
  
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    Generally, the plexus ( Fig. 13.3 ) begins at the cervical spinal cord, through the cervicoaxillary canal of the neck, over the first rib, and into the axilla where it splits into the distal nerves described later in this chapter.

    
    
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    The brachial plexus is divided into five sections as it courses distally ( Fig. 13.3 )

    
    
    
    
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      Three trunks: superior (C5, C6), middle (C7), inferior (C8, T1)

      
      
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      Six divisions: three anterior, three posterior

      
      
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      Three cords: lateral, posterior, medial

      
      
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      Five branches ( Fig. 13.4 )

      
      
      
      
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        Axillary (C5, C6)

        
        
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        Musculocutaneous (C5, 6, 7)

        
        
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        Radial (C5, 6, 7, 8 T1)

        
        
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        Median (C5, 6, 7, 8, and T1)

        
        
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        Ulnar (C7, 8, and T1)

      
      

    
    

  
  

  
  

  
  

  

  
  

  
  

  Anatomy of the distal terminal branches of the brachial plexus demonstrating the general course of the median, musculocutaneous, and radial nerves. Additional demonstration of the sensory cutaneous innervation of the hand, forearm, and distal arm.

  
  

  ((courtesy Netter Atlas of Human Anatomy , Elsevier 2006). From: Netter FH. Atlas of Human Anatomy . Philadelphia, PA: Saunders/Elsevier, 2006. Image 49382.)

  
  
  
  
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  Motor function

  
  
  
  
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    The brachial plexus provides motor function to all the muscles of the arm with the exception of the trapezius muscle (supplied by spinal accessory muscle).

  
  
  
  
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  Sensory function ( Fig. 13.6 )

  
  
  
  
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    The brachial plexus supplies all of the nerves of the skin with the exception of the skin near the axilla, which is supplied by the intercostobrachial nerve.

  
  

  
  

  
  

  

  
  

  
  

  Color-coded illustration of the cutaneous sensory territories of the shoulder, arm, forearm, and hand with inclusion of distal cutaneous nerves of the brachial plexus.

  
  

  ((courtesy Netter Atlas of Human Anatomy 2006). From: Netter FH. Atlas of Human Anatomy . Philadelphia, PA: Saunders/Elsevier, 2006. Image 59208.)

  
  

Procedure:

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  Interscalene approach

  
  
  
  
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    Patient position ( Fig. 13.7 )

    
    
    
    
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      Supine with the head of bed raised approximately 45 degrees

      
      
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      Head is turned contralateral to the injection site

    
    

    
    

    
    

    

    
    

    
    

    Image demonstrating optimal procedure positioning of patient, ultrasound probe, and needle for interscalene approach to the brachial plexus.

    
    

    (From: Waldman SD. Chapter 49: Brachial Plexus Block. In: Waldman SD, ed. Atlas of Interventional Pain Management , 5th edn. Elsevier; 2021: 233-241.)

    
    
    
    
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    Transducer position ( Fig. 13.7 )

    
    
    
    
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      Transducer on the lateral neck near the clavicle behind the clavicular head of the sternocleidomastoid

    
    

  
  

Tip: It can be difficult to find the nerves when directly applying the ultrasound at the interscalene position. This can be helped by finding the brachial plexus at the supraclavicular position, identifying the brachial plexus around the subclavian artery and tracing them to the interscalene position.

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    Ultrasound image ( Fig. 13.8 )

    
    
    
    
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      Cervical nerve roots C5, 6, 7 are visualized between the anterior and middle scalene muscles

      
      
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      The needle is inserted in-plane from lateral to the medial and will pierce the middle scalene muscle on its course to the target nerves.

    
    

    
    

    
    

    

    
    

    
    

    Ultrasound image of the interscalene approach to the brachial plexus. Cervical nerves 5,6,7 can be seen between the anterior and middle scalene muscles.

    
    

    (From: Waldman SD. Chapter 49: Brachial Plexus Block. In: Waldman SD, ed. Atlas of Interventional Pain Management , 5th edn. Elsevier; 2021: 233-241.)

    
    
    
    
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    Sensory distribution ( Fig. 13.9 )

    
    

    
    

    
    

    

    
    

    
    

    Sensory distribution of nerves (C5, 6, 7) accessible from the interscalene approach to the brachial plexus.

    
    

  
  

This approach generally covers the shoulder and upper arm. It is very difficult to reach the inferior trunk (C8–T1) via this approach, so sensation of the medial arm and forearm are spared.

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  Supraclavicular approach –

  
  
  
  
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    Patient position ( Fig. 13.10 )

    
    

    
    

    
    

    

    
    

    
    

    Image demonstrating proper ultrasound position above the clavicle with clavicle outlined.

    
    

    (From: Oliver-Fornies P, Espinosa Morales K, Fajardo-Pérez M, et al. Modified supraclavicular approach to brachial plexus block. J Clin Anesth . 2022;76:110585.)

    
    
    
    
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    Same as interscalene.

    
    
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    Transducer position ( Fig. 13.10 )

    
    
    
    
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      The transducer is placed just above the medial clavicle and tilted caudally to visualize a cross-section of the subclavian artery.

    
    
    
    
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    Ultrasound image ( Fig. 13.11 )

    
    
    
    
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      The brachial plexus is approached at the level of the cords which are seen as a cluster of hypoechoic circles posterior and superficial to the subclavian artery (sometimes referred to as the “cluster of grapes”).

      
      
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      The hypoechoic shadow beneath the subclavian is the first rib.

      
      
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      The pleura is the thin white line in the image lateral to the rib.

      
      
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      Needle approach is in plane lateral to medial.

    
    

    
    

    
    

    

    
    

    
    

    Ultrasound image showing the brachial plexus running between the middle scalene muscle and subclavian artery with the first rib below. The first rib can serve as a backstop to prevent needle placement into the pleura and avoid potential pneumothorax. MSM – middle scalene muscle, SA – subclavian artery, BP – brachial plexus, 1st rib, pleura.

    
    

    (From: Oliver-Fornies P, Espinosa Morales K, Fajardo-Pérez M, et al. Modified supraclavicular approach to brachial plexus block. J Clin Anesth . 2022;76:110585.)

    
    

  
  
  
  
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  Sensory distribution ( Fig. 13.12 )

  
  

  
  

  
  

  

  
  

  
  

  Sensory distribution of nerves blocked at the supraclavicular position.

  
  

The upper extremity distal to the shoulder. Does not anesthetize skin innervated by the intercostobrachial nerve that branches from T2 and innervates the proximal, medial arm.

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  Infraclavicular approach

  
  
  
  
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    Patient position ( Fig. 13.13 )

    
    
    
    
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      Supine with the head of bed raised approximately 45 degrees

      
      
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      Head is turned contralateral to the injection site

      
      
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      Target nerves can occasionally be below the clavicle which can be improved by abducting the arm above the head

    
    

    
    

    
    

    

    
    

    
    

    Image demonstrating positioning of patient, ultrasound, and needle for infraclavicular approach.

    
    

    (From: Gray TA. Chapter 32 – Infraclavicular Block. In: Gray TA, ed. Atlas of Ultrasound-Guided Regional Anesthesia , 3rd edn. Elsevier; 2019: 93-103.)

    
    
    
    
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    Transducer position ( Fig. 13.13 )

    
    
    
    
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      The transducer is placed parasagittally inferior to the clavicle and medial to the coracoid process.

    
    
    
    
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    Ultrasound image ( Fig. 13.14 )

    
    
    
    
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      The axillary artery and vein are landmark structures that reside underneath the pectoralis major and minor muscles. The axillary artery is usually the smaller, noncompressible hypoechoic structure that lies lateral to the axillary vein which is the larger and compressible, hypoechoic structure.

      
      
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      The brachial plexus is seen at the level of the cords which surround the axillary artery. Each cord is named for its relationship to the axillary artery—lateral, posterior, and medial.

    
    

    
    

    
    

    

    
    

    
    

    Ultrasound image of infraclavicular approach to the brachial plexus. PM – Pectoralis Major, PMi – Pectoralis Minor, AA – axillary artery. AV – axillary vein. L – lateral cord. P – posterior cord. M – Medial Cord.

    
    

    (Ultrasound-guided brachial plexus blocks, Pavan Kumar B C Raju, David Mcoventry, Volume 14, Issue 4, August 2014, Pages 185-191, https://doi.org/10.1093/bjaceaccp/mkt059 .)

    
    
    
    
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    Sensory distribution ( Fig. 13.15 )

    
    

    
    

    
    

    

    
    

    
    

    Sensory distribution of nerves affected by the infraclavicular block.

    
    

  
  

The sensory distribution of this approach is the arm below the shoulder excluding the territory of the intercostobrachial nerve.

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  Axillary approach

  
  
  
  
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    Patient position ( Fig. 13.16 )

    
    
    
    
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      Patient is supine with the arm abducted 90 degrees and flexed at the elbow.

    
    

    
    

    
    

    

    
    

    
    

    Image demonstrating positioning of patient, ultrasound, and needle for axillary approach to the brachial plexus.

    
    

    (From: Johnson RL, Kopp SL, Kessler J, Gray AT. Chapter 46: Peripheral Nerve Blocks and Ultrasound Guidance for Regional Anesthesia. In: Gropper MA, ed. Miller’s Anesthesia , 9th edn. Elsevier;2020: 1450-1479.)

    
    
    
    
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    Transducer position ( Fig. 13.16 )

    
    
    
    
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      Transducer is placed in the axilla, perpendicular to the axis of the arm.

    
    
    
    
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    Ultrasound image ( Fig. 13.17 )

    
    
    
    
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      The axillary artery serves as a landmark for orientation and serves as the central point of the neurovascular bundle.

      
      
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      The neurovascular bundle containing the brachial plexus is surrounded by the biceps (anterior and superficial), coracobrachialis (anterior and deep), and conjoined tendon of teres major and latissimus dorsi (medial and posterior).

      
      
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      The brachial plexus is seen at the level of when the cords become terminal nerves with the median (superficial and lateral), ulnar (superficial and medial), and radial nerve (posterior and deep) coursing in parallel with the artery.

      
      
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      The musculocutaneous nerve can be seen in the coracobrachialis muscle.

      
      
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      The axillary and musculocutaneous nerves branch off the plexus at the level of the coracoid process.

      
      
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      The axillary nerve branches laterally and dorsally from the posterior cord.

      
      
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      The medial antebrachial cutaneous nerve runs parallel to the median nerve in the neurovascular sheath.

      
      
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      The needle is inserted anterior to posterior towards the axillary artery.

      
      
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      This position allows access to the proximal median, ulnar, or radial nerves.

    
    

    
    

    
    

    

    
    

    
    

    Ultrasound image of axillary approach to the brachial plexus. AA – axillary artery. AV – axillary vein. MN – Medial nerve. UN – ulnar nerve. RN – radial nerve. McN – Musculocutaneous nerve.

    
    

    (From: Jones MR, Novitch MB, Sen S, et al. Upper extremity regional anesthesia techniques: A comprehensive review for clinical anesthesiologists. Best Pract Res Clin Anaesthesiol . 2020;34(1):e13-e29.)

    
    
    
    
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    Sensory distribution ( Fig. 13.18 )

    
    
    
    
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      Innervates the arm from the mid-arm down.

    
    

    
    

    
    

    

    
    

    
    

    Sensory distribution of nerves affected by the axillary approach to the brachial plexus.