The International Association for the Study of Pain (IASP) defines pain as “An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage.”¹ They further note that pain is affected by biological, social, and psychological factors,¹ which means that sustaining an injury alone is not enough to warrant pain; pain is much more complex than that. In this article, we review the processes involved in pain and different types of pain.

Mechanisms of Pain

When a stimulus damages or threatens to damage tissue (i.e., noxious stimulus), nociceptors, a type of sensory neuron that is part of the peripheral nervous system (PNS), detect the stimulus; this is known as nociception.^1,2 Nociception and pain are not the same thing, as pain cannot be inferred from activation of nociceptors alone; it requires higher brain processing and the experience of numerous other inputs, such as emotional and sensory experience, immune variables, and attention, among others.^1,2 There are two categories of nociceptors involved in pain: myelinated A-delta fibers, which quickly transmit acute, well-localized pain, and unmyelinated C-fibers, which slowly convey continuous, poorly localized pain.^2,3 Once nociceptors receive a stimulus, they transmit signals to the dorsal horn of the spinal cord, which then provides information on the location and intensity of the noxious stimulus to the brain. The flow of information from nociceptors to the brain is known as the ascending pathway.^2,3

The ascending pathway initiates conscious perception of pain, whereas the descending pathway, or the flow of information from the brain to rest of the body, is responsible for moderating pain.² Neurons in the periaqueductal gray (PAG) and rostral ventral medulla (RVM) regulate the output of the spinal cord.^2,3 The spinal cord then releases hormones or chemicals that either inhibit or excite the sensation of pain.² The type of response depends upon a multitude of factors, including cognitive appraisal of the situation, beliefs, social norms, emotional and psychophysiological reactions, previous experience, and expectations.^2,4

Types of Pain

The IASP defines three broad categories of pain: neuropathic, nociceptive, and nociplastic.

Neuropathic pain. Neuropathic pain is “caused by a lesion or disease of the somatosensory nervous system.”¹ It is typically a result of damaged nerve fibers or nerve impairment that leads to spontaneous hyperexcitability of neurons or alterations in their properties.^2,3

Neuropathic pain can be further classified as either central or peripheral neuropathic pain, depending on whether the pain stems from the central nervous system (CNS) or PNS.^1,5 Causes of central neuropathic pain include strokes, traumatic spinal cord injuries, spinal cord compression, and neuralgia. Causes of peripheral neuropathic pain include peripheral neuropathy (e.g., diabetic neuropathy, posttraumatic neuropathy, ischemic neuropathy, cancer-related neuropathies), phantom limb pain, and postherpic neuralgia (following herpes zoster infection).⁶

Neuropathic pain can consist of negative (e.g., numbness, sensory loss) and positive symptoms (e.g., spontaneous pain, increased pain sensation).⁶ It is often chronic^2,7 and can causes burning, sharp, shooting, aching, shock-like, or pins-and-needles-like sensations.^5,6 Further possible symptoms include pain being worse at night and disturbing sleep, associated psychological affect, high severity and irritability, and delayed response to movement or mechanical stressors.⁵

Neuropathic pain is associated with allodynia, or pain occurring due to typically nonpainful stimuli (e.g., feeling pain at a light touch). Allodynia is thought to arise due to damage to peripheral nerves that causes reorganization of touch-sensitive fibers to reroute and send inputs to areas of the spinal cord that typically receive inputs from nociceptors.^2,3

Nociceptive pain. Nociceptive pain “arises from actual or threatened damage to non-neural tissue and is due to the activation of nociceptors.”¹ This pain acts as a defense mechanism, telling us to get away from the source of pain. When we touch a hot stove, experiencing nociceptive pain alerts our body to the danger of the stove, allowing us to react and take our hand away from the noxious stimulus.⁷

Nociceptive pain can be acute or chronic⁷ and is typically categorized as either somatic or visceral. Somatic pain is caused by stimulation of nociceptors (predominately A-delta fibers) that is often described as sharp and localized.^2,3,7 Somatic pain can be further split into superficial and deep somatic pain. The former occurs in cutaneous tissue (e.g., skin) and is often described as sharp, burning, and well localized. The latter occurs in deep tissue (e.g., ligaments, tendons, bones) and is often described as throbbing, aching, and less localized than superficial somatic pain.^2,5 Cuts, burns, fractures, and musculoskeletal pain are examples of somatic pain.⁷ Visceral pain occurs in internal organs due to the stimulation of C-fibers. This pain is described as dull and poorly localized.^2,3

Nociplastic pain. Nociplastic pain “arises from altered nociception despite no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors or evidence for disease or lesion of the somatosensory system causing the pain.”¹ An IASP task force recently released clinical criteria for nociplastic pain in the musculoskeletal system, which entails the following:

• Pain lasting three months or longer
• Regional, not discrete, distribution of pain
• No evidence that nociceptive or neuropathic pain are present or, if present, are entirely responsible for the pain
• History of hypersensitivity in the region of pain
• Presence of certain comorbidities, including fatigue, disturbed sleep, cognitive difficulties, and increased sensitivity to light, sound, and/or odors
• Presence of clinical signs of pain hypersensitivity in the region of pain.⁸

Pain can be classified as probable nociplastic pain if an individual meets all the criteria or possible nociplastic pain if they meet criteria A, B, C, and F.⁸ It is important to note that individuals can have a combination of nociplastic and nociceptive or neuropathic pain.^8,9 Increased responsiveness of CNS nociceptors that results in pain hypersensitivity, or central sensitization, is thought to underlie nociplastic pain.^5,8,10 Nociplastic pain is often present in chronic pain conditions, such as fibromyalgia, complex regional pain syndrome type 1, irritable bowel syndrome, and bladder pain syndrome.^7,8

Bottom Line

The mechanisms behind pain are complex, and pain can be experienced in different ways by different people. If you have concerns about pain, talk to a healthcare professional.

Sources

1. International Association for the Study of Pain. Terminology. https://www.iasp-pain.org/resources/terminology/. Accessed 16 Mar 2023.
2. Chen JS, Kandle PF, Murray I, et al. Physiology, Pain. Updated 25 Jul 2022. In: StatPearls [Internet]. StatPearls Publishing; 2022.
3. Yam MF, Loh YC, Tan CS, et al. General pathways of pain sensation and the major neurotransmitters involved in pain regulation. Int J Mol Sci. 2018;19(8):2164.
4. Moseley L. Explainer – what is pain? International Association for the Study of Pain. 2 Nov 2021. https://www.iasp-pain.org/publications/relief-news/article/what-is-pain/. Accessed 16 Mar 2023.
5. Physiopedia. Pain mechanisms. https://www.physio-pedia.com/Pain_Mechanisms. Accessed 16 Mar 2023.
6. Physiopedia. Neuropathic pain. https://www.physio-pedia.com/Neuropathic_Pain. Accessed 16 Mar 2023.
7. Behrends M. Types of pain. Pain Management Education at University of California San Francisco. https://pain.ucsf.edu/understanding-pain-pain-basics/types-pain. Accessed 16 Mar 2023.
8. Kosek E, Clauw D, Nijs J, et al. Chronic nociplastic pain affecting the musculoskeletal system: clinical criteria and grading system. PAIN. 2021;162(11):2629–2634.
9. Shala R. Chronic nociplastic and neuropathic pain: how do they differentiate? PAIN. 2022;163(6):e786.
10. Nijs J, Lahousse A, Kapreli E, et al. Nociplastic pain criteria or recognition of central sensitization? Pain phenotyping in the past, present and future. J Clin Med. 2021;10(15):3203.