Why does pain cause nausea and vomiting?

From the Guidelines

Pain can cause nausea and vomiting through several interconnected physiological mechanisms, and managing these symptoms simultaneously is crucial to improve patient outcomes. Severe pain triggers the autonomic nervous system, specifically activating the sympathetic "fight-or-flight" response, which can disrupt normal digestive processes and lead to nausea 1. Pain also stimulates the release of stress hormones like adrenaline and cortisol, which can slow digestion and contribute to feelings of nausea. Additionally, the brain regions that process pain signals (such as the medulla oblongata) overlap with areas that control nausea and vomiting, creating a direct neurological connection between these sensations.

When managing pain-induced nausea, it's essential to address both symptoms simultaneously. Medications like ondansetron (4-8mg every 8 hours) or promethazine (12.5-25mg every 4-6 hours) can help control nausea, while appropriate pain management with acetaminophen, NSAIDs, or prescribed pain medications can help break the pain-nausea cycle 1. Staying hydrated and taking medications with food (unless contraindicated) may also help minimize nausea symptoms.

Some key considerations for managing nausea and vomiting in patients with pain include:

• Identifying and treating underlying causes of nausea and vomiting, such as constipation, CNS pathology, chemotherapy, radiation therapy, or hypercalcemia 1
• Using antiemetic agents, such as phenothiazines, dopamine receptor antagonists, or serotonin receptor antagonists, to control nausea and vomiting 1
• Considering alternative therapies, such as acupuncture, hypnosis, or cognitive behavioral therapy, for refractory nausea and vomiting 1
• Using cannabinoids, such as dronabinol or nabilone, for chemotherapy-induced nausea and vomiting that is refractory to standard antiemetic therapies 1

The most effective approach to managing pain-induced nausea and vomiting is to use a multimodal treatment strategy that addresses both symptoms simultaneously and incorporates a combination of pharmacologic and non-pharmacologic interventions. By prioritizing patient-centered care and using evidence-based treatments, healthcare providers can improve patient outcomes and reduce the burden of nausea and vomiting associated with pain management 1.

From the FDA Drug Label

Dopamine produces nausea and vomiting by stimulation of the medullary chemoreceptor trigger zone (CTZ) The answer to why pain causes nausea and vomiting is not directly addressed in the provided drug label. However, it can be inferred that pain may stimulate the release of certain chemicals, such as dopamine, which can then stimulate the chemoreceptor trigger zone (CTZ), leading to nausea and vomiting.

• Key points:
  • Dopamine stimulates the CTZ, causing nausea and vomiting.
  • The exact relationship between pain and the stimulation of the CTZ is not explicitly stated in the label. 2

From the Research

Mechanisms of Pain-Induced Nausea and Vomiting

• Pain, particularly when managed with opioid analgesics, can cause nausea and vomiting due to the activation of various central and peripheral sites, including the vomiting center, chemoreceptor trigger zones, cerebral cortex, and the vestibular apparatus of the brain, as well as the GI tract itself 3.
• Opioid medications bind to μ (mu), κ (kappa), or δ (delta) opioid receptors in the brain, spinal cord, and digestive tract, leading to adverse effects such as nausea and vomiting 4.

Incidence and Impact of Nausea and Vomiting

• Approximately 40% of patients may experience nausea and 15%-25% of patients may experience vomiting after opioid administration 4.
• Nausea and vomiting can lead to complications including electrolyte imbalances, malnutrition, and volume depletion, and can also negatively affect quality of life and postoperative recovery 4.
• In patients with sickle cell disease, 50% of subjects experienced nausea or vomiting during acute pain crises, with nausea reported in 25% of admissions and vomiting in 34% of admissions 5.

Treatment and Management Options

• Various medications can be used to treat opioid-induced nausea and vomiting, including serotonin receptor antagonists, dopamine receptor antagonists, and neurokinin-1 receptor antagonists 4.
• Ondansetron has been shown to be more effective than metoclopramide in the treatment of opioid-induced emesis following post-surgical opioids 6.
• The systematic use of metoclopramide with opioid therapy for non-malignant pain in rheumatology can decrease the risk of nausea and vomiting 7.