Navigating Pain Management: The Science Behind Sympathetic Nerve Blocks

1. BACKGROUND: IMPLICATIONS OF THE SYMPATHETIC NERVOUS SYSTEM IN ACUTE AND CHRONIC PAIN STATES

The sympathetic nervous system (SNS) is intricately connected to both acute and chronic pain states. Acute generalized sympathetic activation, as observed during the stress response, can transiently elevate the nociceptive threshold through a complex interplay of neural and endocrine mechanisms (Tsigos and Chrousos, 2002; Milan MJ, 2002).

Given its trophic and immunomodulatory roles, the SNS exerts both pro-inflammatory and pro-nociceptive effects, particularly at the tissue level (Pongratz and Straub, 2014). Regional sympathetic nerve blockade can effectively relieve ischemic pain by interrupting sympathetic outflow. Additionally, this blockade directly disrupts nociceptive transmission from visceral organs, as most general afferent visceral fibers traverse with sympathetic nerves. In certain conditions, such as complex regional pain syndrome (CRPS), the SNS can pathologically contribute to pain, leading to what is termed “sympathetically-mediated pain” (Figure 1) (Crockett and Panickar, 2011; Chen and Zhang, 2015).

Targeted interventional blockade of sympathetic pathways is routinely utilized for the management of ischemic or sympathetically-mediated pain. The anatomical separation of major sympathetic ganglia and plexuses from somatic nerves in the prevertebral and paravertebral regions facilitates percutaneous intervention. When indicated, sympathetic blocks can deliver substantial analgesia without inducing somatic sensory deficits; this blockade of visceral sympathetic outflow shifts the homeostatic equilibrium in the affected region toward parasympathetic dominance, with attendant physiological repercussions (Doroshenko et al., 2024).

2. ANATOMY AND PHYSIOLOGY OF THE SYMPATHETIC NERVOUS SYSTEM: CLINICAL RELEVANCE FOR PAIN MEDICINE

Central sympathetic nuclei reside in the intermediolateral nucleus of the lateral grey column of the spinal cord, extending from T1 to L2-L3, with relevant connections at the cervical level. Their axons exit the spinal cord via the ventral roots, forming white rami shortly after the ventral ramus branches from the spinal nerve. These myelinated white rami travel to either paravertebral or prevertebral ganglia (Figure 2) (Craven J, 2008). Paravertebral ganglia comprise the sympathetic trunk alongside the vertebral column, consisting of 20 to 24 paired, interconnected ganglionic nodes that converge at the coccygeal level to form the unpaired terminal node known as the ganglion impar. At the cervical level, sympathetic ganglia include the superior, middle, and inferior cervical ganglia, which contribute to the innervation of the head, neck, and upper limbs. Prevertebral (preaortic) ganglia organize into plexuses around the major branches of the abdominal aorta, including the celiac, superior mesenteric, and inferior mesenteric ganglia. Preganglionic white rami reach these ganglia after traversing the paravertebral ganglia and abdominopelvic splanchnic nerves (Doroshenko et al., 2024).

Postganglionic fibers exit the ganglia as unmyelinated grey rami, joining somatic nerves or forming visceral nerves that accompany corresponding visceral vascular bundles or join splanchnic nerves. Afferent input to sympathetic ganglia is conveyed via general visceral afferent fibers that transmit pain and reflex sensations from internal organs to the dorsal horn of the spinal cord (Blumberg et al., 1997; McCorry LK, 2007). From sensory receptors in the originating organ, this input follows a pathway to the corresponding sympathetic ganglion and enters a mixed spinal nerve along with white rami, ultimately reaching the dorsal root ganglion (DRG), where the cell body of the general visceral afferent nerve resides. This anatomical arrangement and the spatial separation of sympathetic and somatic nerve structures - particularly at cervical, lumbar, and sacral levels - facilitate selective interventional blockade of sympathetic pathways relaying visceral nociceptive information (Doroshenko et al., 2024).

Sympathetic blockade with local anesthetics is utilized diagnostically to determine if pain is sympathetically mediated. Often, pain relief outlasts the expected duration of the local anesthetic, thereby providing a therapeutic benefit. Adding a depot corticosteroid, when indicated, can extend the effects of sympathetic blockade from days to weeks. Once the block is shown to be effective, chemical neurolysis or ablative techniques may be employed for longer-lasting relief. When proper needle placement is confirmed radiographically/ultrasonographically (Figure 3) and significant analgesia is achieved using a low concentration of local anesthetic - without signs of sensory or motor blockade - it is inferred that the effects resulted from the sympathetic block. However, larger volumes of anesthetic are more likely to affect nearby somatic nerves, potentially leading to a false-positive result (Day M, 2008; Doroshenko et al., 2024).

3. SYMPATHETIC NERVE BLOCKS IN PAIN MEDICINE: TARGETED CLINICAL APPLICATIONS

Diagnostic sympathetic blocks serve as pivotal tools to confirm the presence of sympathetically mediated pain. For prolonged therapeutic effect, neurolytic agents or repeated administrations of local anesthetics can be employed. Advanced physical modalities, including radiofrequency denervation and cryo-neurolysis of sympathetic nerves, provide additional avenues for sustained relief. Sympathetic blocks are clinically indicated for the management of complex visceral, vascular, and neuropathic pain syndromes (Figure 4) (Craven J, 2008; Doroshenko et al., 2024):

• Visceral Pain: The coeliac (celiac) plexus innervates foregut and midgut structures, including the stomach, duodenum, pancreas, biliary system, liver, and small intestine. Blocking this plexus can relieve pain and nausea associated with malignancies in these organs, potentially reducing or eliminating the need for opioid therapy. Relief may last for weeks to months if neurolytic agents are used, and celiac plexus blocks can be repeated if symptoms recur, although the duration of relief may diminish with repeated procedures (Bahn and Erdek, 2013; Doroshenko et al., 2024). The superior hypogastric plexus innervates hindgut structures, such as the descending and sigmoid colon, and pelvic organs like the uterus, ovaries, and prostate. Blocking this plexus is effective for treating persistent pelvic and rectal pain that has not responded to conservative measures (Figure 3) (Bosscher H, 2001). The inferior hypogastric plexus block addresses pelvic, perineal, and genital pain, but it is less commonly used due to its challenging anatomical location and associated risks (Doroshenko et al., 2024). Distal pelvic structures are innervated by the ganglion impar, which can be targeted for malignant vulvar, rectal, and anal pain, as well as intractable sacral pain conditions like postherpetic neuralgia and coccydynia (Scott-Warren et al., 2013; Doroshenko et al., 2024). The thoracic paravertebral sympathetic chain, while transmitting nociceptive input from thoracic viscera, is rarely blocked due to complex anatomy and higher complication risks (Doroshenko et al., 2024). If the primary disease process involves somatic structures (e.g., malignancy invading abdominal walls or musculoskeletal tissues, nerves), and the pain gains a somatic component, a sympathetic block may be less efficacious. In such cases, regional and neuraxial techniques may improve the quality of pain relief. Neuraxial analgesia (intrathecal or epidural) will block somatic and visceral afferents simultaneously, which is the basis for the implantation of long-term intrathecal drug delivery systems (Doroshenko et al., 2024);
• Neuropathic Pain: Sympathetic blocks can provide significant, though often incomplete, relief from neuropathic pain and are typically used in conjunction with adjuvant therapies such as physiotherapy, medications, and neuromodulation. Their role in treating acute herpes zoster pain is uncertain; however, stellate ganglion blocks may reduce the risk of postherpetic neuralgia in cases affecting the trigeminal region (Makharita et al., 2012). For herpes zoster affecting the trunk and extremities, epidural or paravertebral injections of local anesthetics and corticosteroids are generally more effective (Hwang et al., 1999; Doroshenko et al., 2024). The efficacy of sympathetic blocks for postherpetic neuralgia remains controversial, with limited evidence supporting their use in conditions like painful diabetic neuropathy. Phantom limb pain is thought to be partially sympathetically mediated, and while some studies suggest sympathetic blocks may relieve stump pain, more research is needed (Cohen et al., 2011). According to guidelines from the American Society of Anesthesiologists (ASA) and the American Society of Regional Anesthesia and Pain Medicine (ASRA), sympathetic nerve blocks are not recommended for chronic neuropathic pain unrelated to complex regional pain syndrome (CRPS) (Doroshenko et al., 2024). Nonetheless, sympathetic blockade can be beneficial in CRPS, where pain is often maintained by hypersensitivity to norepinephrine from sympathetic efferents. This condition affects approximately one-third of CRPS patients, and both stellate ganglion and lumbar sympathetic blocks with local anesthetics and adjuvants like clonidine and steroids are indicated when conservative treatments fail. In cases where sympathetic blocks provide temporary relief, neurolysis or ablation of the lumbar plexus may offer longer-lasting pain management (Cheng et al., 2019; Doroshenko et al., 2024);
• Vascular Pain: Pain from tissue ischemia (e.g., vasospastic, thrombotic, or embolic) is transmitted via sympathetic afferent fibers and is enhanced by sympathetic vasoconstriction. Simultaneously, chronic ischemia can directly damage soft tissues (e.g., ulceration) and nerves, adding somatic and neuropathic nociceptive components, respectively. Lumbar sympathetic block for treating resting pain of obliterative lower extremity disease (e.g., thromboangiitis obliterans and atherosclerosis) was historically among the most beneficial neural percutaneous interventions available. Most patients responded with significantly decreased pain and increased perfusion in the affected extremity (Alexander JP, 1994; Doroshenko et al., 2024). Neural ablation or denervation of the lumbar chain in these patients facilitates exercise and rehabilitation, leading to lasting improvement. Pain from chronic vasospastic disease (e.g., Raynaud's syndrome, acrocyanosis, livedo reticularis, sequelae of poliomyelitis, and spinal cord injury) and cold injury are quite responsive to sympathetic blocks as well (Landry GJ, 2013; Doroshenko et al., 2024).

Common subjective signs of sympathectomy include pain relief, warmth, decrease in perspiration, and change in color of the area supplied by the nerves blocked. Objective tests are recommended and include measuring skin temperature (expected to elevate for the ipsilateral limb compared to the contralateral limb) and blood flow, skin conductance, and provocative sweat tests (eg, cobalt blue or ninhydrin sweat tests) (Tran et al., 2000; Doroshenko et al., 2024). Horner's triad (ipsilateral partial ptosis, myosis, and facial anhydrosis) is a sign of sympathectomy at the inferior cervical (stellate) ganglion level. Yet, it does not always correlate with adequate pain relief of the upper extremity. Note that the upper extremity receives some of its sympathetic efferents from the upper thoracic ganglia, which the anesthetic from the stellate ganglion block may not reach (Doroshenko et al., 2024).

4. CONTRAINDICATIONS FOR SYMPATHETIC NERVE BLOCKS: KEY CONSIDERATIONS FOR CLINICAL PRACTICE

The known allergy to medications planned to be used and refusal or inability to cooperate and consent are absolute contraindications. Infection or malignancy with loci along the needle path is a relative contraindication due to the risk of dissemination. Anticoagulation and coagulopathy diagnoses should be addressed and treated according to ASRA guidelines before a sympathetic block, considering the proximity of the sympathetic ganglia to major vascular structures (Narouze et al., 2018).

Preexisting motor and sensory deficits, concordant with the area of the block, should be thoroughly documented, and the possibility of delaying the block until improvement of symptoms, if feasible, should be discussed. Patients on antihypertensive medications of any class, especially those on diuretics, may develop more severe hypotension than those without hypertension (Doroshenko et al., 2024). Visual alterations after stellate ganglion block have been described; thus, the availability of an escort post-procedure is essential. Bowel peristalsis may increase after celiac block, an important consideration for patients predisposed to bowel obstruction (Doroshenko et al., 2024).

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