What are pain pathways (nociceptive pathways)?

From the Guidelines

Pain pathways are complex neural routes that transmit pain signals from the site of injury to the brain for processing, involving nociceptors, first-order neurons, spinal cord, and brain regions such as the thalamus, somatosensory cortex, limbic system, and prefrontal cortex. These pathways begin with nociceptors (pain receptors) in the skin, muscles, and organs that detect harmful stimuli like heat, pressure, or chemicals, as defined by the International Association for the Study of Pain (IASP) 1. When activated, these receptors generate electrical signals that travel through first-order neurons to the spinal cord via A-delta fibers (fast, sharp pain) or C fibers (slow, dull pain) 1. In the spinal cord, these neurons synapse with second-order neurons in the dorsal horn, which cross to the opposite side and ascend to the brain through the spinothalamic tract. The pain signals then reach the thalamus, which directs them to various brain regions including the somatosensory cortex (for pain localization), the limbic system (for emotional responses), and the prefrontal cortex (for cognitive processing) 1.

Some key points to consider about pain pathways include:

• Nociception is the neural process of encoding and processing noxious stimuli, which can provoke either acute pain or chronic pain 1
• The disruption of tissue integrity increases the discharge rate of nociceptive neurons and initiates a local inflammatory response sustained by a cascade of mediators and activation of immune cells 1
• Inhibitory interneurons play an important modulatory role, limiting the flow of nociceptive information to supraspinal areas, and utilizing different neurochemical classes of neurotransmitters/neuropeptides, including cholinergic, opioidergic and GABAergic interneurons 1
• Descending pathways originating in the brainstem and in other cerebral structures, such as the rostral ventromedial medulla (RVM), periaqueductal grey (PAG) and hypothalamus, modulate the nociceptive information at the spinal dorsal horn mainly by reducing the release of neurotransmitters from primary afferent neurons or by inhibiting projection neurons and excitatory interneurons 1

The body can modulate these signals through descending pathways from the brain that release endorphins and other neurotransmitters to reduce pain perception, which is how many pain medications work by enhancing these natural pain-suppressing mechanisms 1. Overall, understanding pain pathways is crucial for developing effective pain management strategies that target the complex neural mechanisms involved in pain perception.

From the Research

Overview of Pain Pathways

Pain pathways involve a complex interplay between messages sent from the periphery to the central nervous system and vice versa, with specific pathways playing a vital role in carrying these messages and modulating their downstream effects 2. The pain pathways can be described as follows:

• The nociceptive pathway consists of a classic three-neuron chain, which is now understood to be a dual system at each level, with the discriminative component of pain ("first pain") carried separately from the affective-motivational component of pain ("second pain") 3.
• The sensation of pain arrives in the central nervous system through ascending pathways, while descending pathways that originate in the cortex, thalamus, and brain stem can modify functions at the spinal level 3.
• There is a close relationship between somatic pain pathways and visceral pathways, which likely accounts for the transmission of visceral pain and autonomic responses to somatic pain and somatic responses to visceral pain 3.

Anatomy and Physiology of Pain Pathways

The anatomy and physiology of pain pathways involve the transmission and parcellation of noxious stimuli from the peripheral nervous system to the central nervous system 4. Key aspects include:

• The role of peripheral nociceptors in detecting noxious stimuli and transmitting signals to the central nervous system 5.
• The inhibitory and excitatory systems that regulate pain, including the consequences of dysfunction 4.
• The central nervous system areas involved in the perception and modulation of pain, including the brain stem, thalamus, and cortex 5.

Types of Pain and Molecular Targets

There are several types of persistent pain, including neuropathic and inflammatory persistent pain, which involve different molecular targets 5. These targets include:

• Ion channels, which play a crucial role in the transmission of pain signals 5.
• Receptors, which are involved in the modulation of pain signals 5.
• Neurotransmitters, which are released by neurons to transmit pain signals 5.