The autonomic nervous system (ANS) controls essential physiological functions, including heart rate, blood pressure, digestion, respiration, pupillary reactivity, sweating, urination, and sexual arousal. It plays a vital role in maintaining homeostasis across cells, tissues, and organs, and helps the body respond to internal and external stressors. The ANS comprises three main divisions: the sympathetic nervous system (SNS), the parasympathetic nervous system (PNS), and the enteric nervous system.
The sympathetic system mediates the "fight or flight" response and primarily involves adrenergic receptors (alpha and beta), with muscarinic receptors present in sweat glands. In contrast, the parasympathetic system governs the "rest and digest" response, utilizing muscarinic and nicotinic acetylcholine receptors at target organs.
Pain regulation involves descending pathways that exert modulatory effects through aminergic neurotransmitters. Key structures involved in this regulation include the hypothalamus, amygdala, and periaqueductal gray (PAG). Dysfunction of the ANS is commonly observed in patients with chronic pain and may involve either the sympathetic or parasympathetic branches (Arslan et al., 2022). The ANS plays a central, bidirectional role in both the experience and regulation of pain. Neural circuits responsible for pain processing are closely integrated with autonomic pathways, sharing anatomical and functional networks. Brain regions such as the anterior cingulate cortex (ACC), amygdala, and PAG—crucial for autonomic control—are consistently activated during pain experiences (Hohenschurz-Schmidt et al., 2020).
Painful stimuli trigger a cascade of autonomic responses, including increased respiratory rate, muscle tension, electrodermal activity, and pupillary dilation. These effects are primarily mediated by sympathetic activation, resulting in elevated heart rate, blood pressure, sweating, and vasoconstriction. Although parasympathetic activation generally opposes these effects, the interaction between both branches is dynamic and context-dependent rather than purely antagonistic (Kyle & McNeil, 2014).
Notably, the ANS contributes not only to immediate pain responses but also to the persistence and amplification of pain, particularly in chronic conditions. In acute pain, coordinated activation of the ANS and hypothalamic-pituitary-adrenal (HPA) axis supports adaptive responses and restores homeostasis. However, in chronic pain or prolonged stress, repeated activation of these systems leads to maladaptive neuroplastic changes, heightening pain sensitivity and disrupting regulatory balance (Yeater et al., 2022).
In neuropathic pain, the ANS is also implicated at the peripheral level. Nerve injury can alter the local environment, triggering activation and reorganization of satellite glial cells and autonomic neurons. These changes—including axonal sprouting, altered ion channel expression, and structural reorganization—can perpetuate or intensify pain signaling (Meacham et al., 2017).
Furthermore, the emotional dimension of pain is closely tied to autonomic function. Anxiety, often comorbid with chronic pain, is a stress-induced state mediated through autonomic pathways. Chronic stress and anxiety can disrupt neurotransmitter systems, impair synaptic plasticity, and alter levels of neurotrophins—factors that further entrench pain experience (Zietek et al., 2014).
Sympathetic blocks (SB) are frequently used when elevated sympathetic nervous system activity contributes to spontaneous pain or hyperalgesia.
The stellate ganglion block (SGB), targeting the sympathetic ganglion in the lower cervical/upper thoracic region, can provide pain relief in the head, neck, and upper extremities. However, due to its anatomical location near vital structures such as the lungs and thyroid gland, the procedure carries a risk of complications, including pneumothorax and thyroid injury. Imaging-guided techniques (ultrasound, fluoroscopy, CT) are preferred to minimize risk (Zhu et al., 2019). Jeon et al. (2016) highlighted the efficacy of SGB in managing orofacial pain and complex regional pain syndrome (CRPS) following craniofacial trauma. Other indications include intractable facial pain, postherpetic neuralgia, and burning mouth syndrome.
The sphenopalatine ganglion block (SPG) targets parasympathetic and some sympathetic fibers innervating facial structures. SPG blockade is a safe and effective treatment for chronic headache disorders, including cluster headaches, migraines, and other trigeminal autonomic cephalalgias (Mojica et al., 2017).
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