What is the neurotransmitter that transmits pain in the spinal cord?

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From the Guidelines

Substance P is the primary neurotransmitter responsible for transmitting pain signals in the spinal cord. This neuropeptide is released from primary afferent nerve fibers when they are activated by painful stimuli, as described in the study by Millan (1999) 1. Once released into the dorsal horn of the spinal cord, Substance P binds to neurokinin-1 receptors on second-order neurons, initiating the transmission of pain signals up the spinothalamic tract to the brain.

Key Points

  • Glutamate also plays an important supporting role in this process, often co-released with Substance P to enhance pain transmission, as mentioned in the study 1.
  • Understanding this mechanism is crucial because it explains how certain pain medications work, such as those that block the release or action of Substance P to help reduce pain perception.
  • Chronic pain conditions may involve sensitization of this pathway, leading to heightened pain responses even to normally non-painful stimuli, as discussed in the context of chronic pain by Raffaeli and Arnaudo (2017) and Humo et al. (2019) 1.

Neurotransmitters Involved

  • Substance P: primary neurotransmitter for pain transmission
  • Glutamate: supporting role in pain transmission
  • Other neurotransmitters like 5-hydroxtryptamine (5-HT, serotonin), noradrenaline, and dopamine play a role in modulating pain transmission, particularly in the context of descending pathways from the brainstem and other cerebral structures 1.

From the Research

Neurotransmitters Involved in Pain Transmission

  • The neurotransmitter that transmits pain in the spinal cord is substance P 2, 3, 4, 5.
  • Substance P is released from primary afferent fibers and acts on nociceptive projection neurons in the dorsal horn of the spinal cord 2, 3.
  • Other neurotransmitters such as gamma-aminobutyric acid (GABA) and enkephalins also play a role in modulating pain inputs in the spinal cord 2.

Mechanisms of Pain Transmission

  • The spinal cord is the first relay site in the transmission of nociceptive information from the periphery to the brain 6.
  • Sensory signals are transmitted from the periphery by primary afferent fibers into the dorsal horn of the spinal cord, where they synapse with intrinsic spinal dorsal horn neurons 6.
  • Spinal projection neurons then convey this information to higher centers in the brain, where non-noxious and noxious signals can be perceived 6.

Role of Substance P in Pain Transmission

  • Substance P serves as a pain transmitter in a subpopulation of primary afferent C fibers 2.
  • Substance P-driven feed-forward inhibitory activity in the dorsal horn plays a role in modulating sensory processing and affecting sensory perception by the brain 5.
  • The inhibition of substance P release by μ-opioid receptors is lost in neuropathic pain but not in inflammatory pain 4.

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

2
Research

Pain and neurotransmitters.

Cellular and molecular neurobiology, 1990

6
Research

Spinal cord mechanisms of pain.

British journal of anaesthesia, 2008

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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