In many cases, the initial stimulus for pain is the destruction or injury of tissue adjacent to certain nerve fibers. The damaged tissue releases chemicals that activate pain fibers in the skin. Various substances have been suggested as the chemical mediators of pain, including neuropeptides, serotonin, histamine, various proteolytic enzymes, and prostaglandins.

Johns Hopkins University

Pain, although in some aspects emotional, can find its basis in the physiological occurrences of the human body.
- Damaged Tissue and Chemical Release
- Nociceptors
- Specialized Pain Fibers
- Pain in the Spinal Pathways
- Cortical Substrates for Pain
- Neuropathic Pain and Phantom Limbs
- The Pain of Social Rejection 
- Controlling Pain

Biological Basis of Pain

Breedlove, S. & Watson, N. (2017). Behavioral neuroscience, eighth edition. Oxford University Press.

Behavioral Neuroscience 8th Edition

Damaged Tissue and Chemical Release

Sensations of pain and temperature are transmitted separately by the anterolateral, or spinothalamic, system.
- Anterolateral System
- Glutamate
- Substance P

Pain in the Spinal Pathways


Pain that sustains after a peripheral nerve injury is called neuropathic pain, also known as neuralgia. After peripheral injuries, microglial cells surround the synapses between pain fibers and neurons in the dorsal horn of the spinal cord, releasing chemicals that make the dorsal horn neurons hyper-excitable. This leads to neural signaling of pain in the hypothalamus. 

Cases of neuropathic pain can be considered disagreeable examples of neural plasticity since the nervous system (either the spinal cord or the cortex) amplifies its response to the pain signal. 

• Phantom Limb Pain 

• Migraines 


Neuropathic Pain 

Peripheral receptors and nerve fibers that respond to pain. There are 3 different kinds of painful stimuli nociceptors can be attuned to: chemical, physical, and thermal. Some nociceptors respond to itch sensations. 
- TRPV1 (temperature)
- TRMP3 (higher temperature)
- CMR1 (cold)
- Nppb (itch)
- Nav 1.7 (mechanical pain)

Nociceptors

Anxiety and hurtful feels that arise when one feels excluded (be it a team sport, a dinner party, or a breakup) can be categorized as social pain. In the brain, social rejection is a category of pain that isn’t too different from the pain that we feel after a physical injury, disproving the outdated saying, “Sticks and stones may break my bones, but words will never hurt me.” Gender differences in bullying styles reiterate this ideal – while boys usually resort to physical bullying, girls tend to use social rejection to hurt each other. 
-	Evolutionary Explanations of Pain Associated with Social Rejection
-	Biological Basis of Pain Associated with Social Rejection
-	Tylenol for Pain Associated with Social Rejection 


The Pain of Social Rejection

A variety of treatment options exist for pain relief, including relaxation therapy, analgesic medications, and deep brain stimulation. The selection of the most effective treatment is highly individualized, depending on factors like the pain's severity and persistence, as well as the patient's specific medical and psychological state.

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