Why Does it Hurt so Much Part 1
🔬 Chapter 1: Pain Is a Signal and an Evolutionary Superpower
Let’s start with a bold statement: Pain is good.
Okay, stick with me…
Pain has a bad reputation, but it’s actually essential to our survival.
Evolutionarily, pain is your body’s internal alarm system, warning you when tissues are damaged or about to become damaged. Without it, you could burn yourself, walk on a fractured bone, or worsen a joint injury without realizing it.
When pain kicks in, it pushes you to stop doing whatever is harming you, whether putting your hand on a hot surface or trying to climb the stairs with a subluxed knee.
Bottom line: Pain evolved to protect you. It teaches caution, forces rest, and buys your body time to heal.
🧬 The Biology Behind Pain: Nociceptors at Work
Under your skin, inside your muscles, and around your organs are special nerve endings called nociceptors.
These are sensory receptors that detect potentially harmful stimuli, such as:
- Extreme temperature (hot or cold)
- High pressure or mechanical impact
- Chemical changes that occur when tissues are injured or inflamed
Here’s the key point: Nociceptors don’t sense “pain” itself , they sense danger. They pick up on heat, pressure, stretch, or damage. Your brain is the one that takes those danger signals and decides whether to generate the experience of pain.
That means pain isn’t in your joints, skin, or muscles, it’s your brain’s protective interpretation of incoming messages. This is why two people can injure themselves in the same way, but one might feel unbearable pain while the other feels very little: their brains are processing the signals differently.
There are two main types of nociceptor fibers:
- A-delta fibers — thin, myelinated (covered in insulation) nerve fibers that conduct signals quickly. They transmit sharp, immediate pain (“touching a hot stove”).
- C fibers — unmyelinated (bare fibers), slower-conducting fibers that send dull, throbbing, or aching signals (“lingering sunburn or sprain”).
When activated, nociceptors convert those harmful stimuli into an electrical signal (called an action potential, or an electrical pulse that nerves use to send messages), which travels to your spinal cord and then your brain, where the sensation of pain is registered.
Bonus fact: Nociceptors also release chemical messengers that promote inflammation (swelling, redness, and warmth), kicking off the repair process.
🧪 The Chemistry of Pain Signaling
Inside your nervous system, neurotransmitters or chemical messengers that transmit signals between nerve cells, carry pain messages along the pathway to the brain.
One of the most important is glutamate. Glutamate is the primary excitatory neurotransmitter in the central nervous system, meaning it makes receiving nerve cells more likely to fire and pass along the pain message.
When nociceptive signals reach the spinal cord, glutamate is released and binds to specialized proteins on the receiving cells called NMDA receptors and AMPA receptors (protein ‘switches’ on nerves that make pain signals louder and faster).
- NMDA (N-Methyl-D-Aspartate) receptors and AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors are both types of glutamate receptors that increase the strength and speed of pain transmission.
Other important chemical players include:
- Substance P — A neuropeptide that turns up pain perception.
- Calcitonin Gene-Related Peptide (CGRP) — A signaling molecule that contributes to inflammation and pain, especially in migraines.
- Cytokines — Immune system messengers that promote inflammation and can heighten pain sensitivity.
😱 What Happens When You Can’t Feel Pain?
It might sound like a dream for someone living with chronic pain… but it’s actually a nightmare.
Some people are born with congenital insensitivity to pain (CIP), often caused by mutations in the SCN9A gene. This gene codes for a sodium channel (Nav1.7), a kind of molecular “gate” that nerve cells need to fire. Without it, nociceptors can still sense danger in the tissues, but they can’t generate the electrical signals that travel up the nerves.
It’s not that the body isn’t getting hurt, it’s that the brain simply never receives the danger signal.
The consequences can be devastating: children chewing through their tongues and lips without realizing it, or walking on broken bones for days because nothing tells them to stop. In one case, a woman didn’t know she had appendicitis until her appendix ruptured.
Pain, it turns out, isn’t the enemy, it’s a necessary warning system. Without it, injuries pile up silently.
🧩 When the System Glitches
For people with EDS, the problem isn’t a missing alarm, it’s an alarm that goes off too often and too loudly.
Sometimes there’s a clear danger signal: a subluxed joint, an overstretched ligament, a nerve compressed by unstable tissues. Nociceptors in these areas are just doing their job, sounding the alert to say “something might be wrong.”
But here’s where it gets tricky: the brain is the one that decides whether to interpret those signals as pain. In EDS, the constant stream of smaller “danger reports”, from microtraumas during daily movement, mast cell mediators irritating nerve endings, or proprioceptive “error messages” from unstable joints, primes the brain to treat even normal signals as threats.
Over time, the nervous system can get stuck in this high-alert loop. The alarm starts going off at the faintest background noise, not just at real emergencies.
In fact, the brain can even “remember” pain pathways and keep re-firing them even when no active injury exists. This is the same principle behind phantom limb pain: the brain still has a map of a missing limb and continues to generate pain signals, even when the tissue is gone.
In EDS, the result is pain that can feel like it’s everywhere and nowhere at once, magnified, unpredictable, and often disconnected from a visible injury.
The good news? This system isn’t broken forever. With the right inputs, movement, therapy, education, and nervous system retraining, the brain can relearn which danger signals to quiet down and which ones truly deserve an alarm.
🧠 Chapter 2: Types of Pain
Pain isn’t just one thing. It’s more like a family of related experiences, each with its own cause, pathway, and treatment options. Knowing which type(s) you have is key to figuring out what might help, and why a medication or therapy works for one person but not another.
Nociceptive Pain
The “classic” alarm-signal pain, caused by actual tissue injury or inflammation. In EDS, this can come from microtraumas, joint instability, or overuse injuries.
Feels like: aching, throbbing, or sharp with movement.
Best addressed by: reducing inflammation, protecting the injured tissue, and allowing healing time.
Neuropathic Pain
Pain caused by nerve damage, compression, or malfunction. The “wires” themselves are faulty.
Feels like: burning, tingling, electric shocks, stabbing.
Best addressed by: calming overactive nerves (often with specific medications or nerve-focused therapies).
Central Sensitization
A hypersensitive nervous system that overreacts to even mild input. The volume knob is turned way up, and stuck there.
Feels like: widespread pain, tenderness, fatigue, sensory overload.
Best addressed by: retraining the nervous system through education, gradual activity, and regulation techniques.
Visceral & Referred Pain
Pain from internal organs that’s felt elsewhere because the brain can’t precisely map it.
Feels like: pain in unexpected places (e.g., gallbladder pain in the shoulder).
Best addressed by: identifying and treating the underlying organ source.
🧬 Chapter 3: Why Pain Becomes Chronic
Pain is meant to be temporary, a warning system that steps in, gets the message across, and then turns off so you can get back to life. But in chronic pain, the system fails to shut down. Instead, it keeps sounding the alarm long after the original problem has healed. Here’s why that can happen:
Neuroplasticity, The Nervous System Learns Pain Neuroplasticity is the nervous system’s ability to rewire itself, to form new connections between neurons (nerve cells) and strengthen old ones. Normally, this is how we learn new skills or adapt to changes in our environment. But the same process can work against us when it comes to pain.
If pain signals travel the same pathways repeatedly, for example, from ongoing microtraumas in EDS, those pathways get stronger and more efficient. The nervous system essentially “gets better” at producing pain, even if there’s no fresh injury.
This is why some pain can feel like it’s “stuck on repeat.” Your brain isn’t making it up, it’s just been trained, through repetition, to expect and generate pain signals.
Glial Cell Activation, The Amplifiers Glial cells are generally thought of as the nervous system’s support crew. They don’t carry signals like neurons do, but they maintain the environment around neurons, regulate immune responses, and help repair damage.
When there’s an injury or inflammation, glial cells spring into action. That’s good in the short term, they help clean up debris and promote healing. But if they stay chronically activated, they release inflammatory chemicals that make neurons more sensitive.
Think of it like having an overenthusiastic sound engineer constantly cranking up the microphone volume. Everything, even normal background noise, starts to sound painfully loud.
Cytokines & Prostaglandins, Chemical Messengers of Inflammation When tissues are injured, they release cytokines (proteins that signal immune activity) and prostaglandins (lipid-based molecules that increase sensitivity of nociceptors). These are part of your body’s normal healing process.
In acute pain, they help by recruiting immune cells to repair damage. But in chronic pain, especially in conditions like EDS where tissue microtrauma is common, these chemicals will linger. Their constant presence keeps the nervous system primed for pain, like a fire alarm stuck in the “on” position.
Whole-Body Disruption, Pain Doesn’t Stay in One Place Chronic pain isn’t just about one injured spot. It can spill over into almost every system in the body.
- Stress hormones – Persistent pain keeps your stress response activated which raises cortisol levels. This affects sleep, mood, digestion, and immunity.
- Mast cell activation – Mast cells release histamine and other mediators that can irritate nerves directly, increasing pain sensitivity.
- Dysautonomia – Conditions like POTS disrupt heart rate, blood flow, and digestion, which can worsen pain perception and recovery.
In EDS, these systems are already more fragile. Add in a hyperactive pain network, and the whole body can feel “on edge” all the time.
📝 TLDR: Key Takeaways
- Pain is protective: It acts as an evolutionary alarm system, warning you about potential or actual harm. Without it, injuries would go unnoticed.
- Nociceptors = danger detectors: These special nerve endings pick up harmful signals (heat, stretch, chemicals), but your brain decides when you feel pain.
- Neurochemicals amplify signals: Glutamate (fast nerve activator), Substance P (intensity booster), CGRP (inflammation driver), and cytokines (immune messengers) turn up the volume on pain pathways.
- Pain comes in different types:
- Nociceptive pain → from tissue damage or inflammation (aching, throbbing).
- Neuropathic pain → from faulty or irritated nerves (burning, tingling, electric).
- Central sensitization → when the nervous system’s “volume knob” is stuck on max (widespread, unpredictable).
- Visceral/referred pain → from organs but felt in unexpected body areas.
- Why pain becomes chronic:
- Neuroplasticity makes the nervous system better at producing pain the longer signals repeat.
- Glial cells can amplify pain if they stay switched on too long.
- Cytokines & prostaglandins keep nerves sensitized in ongoing inflammation.
- Whole-body effects: stress hormones, mast cells, and dysautonomia (like POTS) worsen the pain experience in EDS.
- CIP (congenital insensitivity to pain) shows why pain is essential: damage still happens, but the brain never gets the message, leading to dangerous unnoticed injuries.
- In EDS, the issue isn’t missing the alarm, it’s an alarm system that keeps misfiring. The brain can mistake normal signals for danger, creating widespread, unpredictable pain.
- The hopeful part: The nervous system can relearn. Through movement, therapy, education, and regulation techniques, the “alarm” can be turned down.
✨ Coming Up Next, Part Two: What Helps, What Doesn’t, and Why
Now that we’ve explored what pain is and why it can become chronic, the next step is figuring out what we can actually do about it.
In Part Two, we’ll break down:
- The science behind different pain treatments, from medications to movement to nervous system retraining.
- Which approaches have solid evidence, and which don’t.
- Why EDS pain needs a different playbook than most chronic pain.
There’s no miracle cure, but there is a way to turn down the volume on the alarm. And understanding your pain is the first, most powerful step.
📚 References & Further Reading
Costigan M, Scholz J, Woolf CJ. Neuropathic pain: A maladaptive response of the nervous system to damage. Annu Rev Neurosci. 2009;32:1–32. PMID: 19400724 Overview of pain mechanisms and nervous system changes in chronic pain.
Ji, Ru-Rong, et al. Neuroinflammation and central sensitization in chronic and widespread pain. Anesthesiology. 2018; 129(2):343-366 PMID: 29462012 In-depth review of how nerve damage and central sensitization occur.
Woolf Clifford J. Central sensitization: Implications for the diagnosis and treatment of pain. Pain. 2011;152(3 Suppl):S2–S15. PMID: 20961685 Foundational paper explaining how the nervous system amplifies pain.
Guerrieri, Viviana, et al. Pain in Ehlers-Danlos Syndrome: A Non-Diagnostic Disabling Symptom? Healthcare (Basel) 2023; 11(7):936 PMID: 37046863 Specific to EDS, covering prevalence and mechanisms of pain.
Fillingim RB, et al. Sex, gender, and pain: A review of recent clinical and experimental findings. J Pain. 2009;10(5):447–485. PMID: 19411059 Discusses gender bias and biological differences in pain perception.
Dowlati MD, Ehsan. Spinal cord anatomy, pain, and spinal cord stimulation mechanisms. Seminars in Spine Surgery. 2017;29(3)136-146. Article Clear explanation of how pain is processed in the spinal cord.
Sikandar, Shafaq, et al. Visceral pain – the Ins and Outs, the Ups and Downs. Curr Opin Support Palliat Care. 2012; 6(1):17-26 PMID: 22246042 The science of referred and visceral pain.
Schubert-Hjalmarsson, Elke et al. Exploring signs of central sensitization in adolescents with hypermobility spectrum disorder of hypermobile Ehlers-Danlos syndrome. Eur J Pain. 2025;29(1):e47542024. PMID: 39529262 Demonstrates that adolescents with hEDS or HSD show measurable signs of central sensitization, reinforcing the role of altered nervous system processing in chronic pain.
Sluka KA, Clauw DJ. Neurobiology of fibromyalgia and chronic widespread pain. Neuroscience. 2016;338:114-129 PMID: 27291641 Reviews the neurobiological mechanisms underlying fibromyalgia and chronic widespread pain, providing a framework for understanding similar central sensitization processes in hEDS.
Van Oosterwijck J, Meeus M, et al. Pain physiology education improves health status and endogenous pain inhibition in fibromyalgia: a double-blind randomized controlled trial. Clin J Pain. 2013;29(10):873-82 PMID: 23370076 Shows that targeted pain physiology education can improve health outcomes and endogenous pain inhibition, highlighting the value of addressing pain processing directly.
Chopra P, Tinkle B, et al. Pain management in the Ehlers-Danlos syndromes. Am J Med Genet C. 2017;175(1):212-219 PMID: 28186390 Summarizes pain mechanisms and multidisciplinary management strategies specific to Ehlers-Danlos syndromes, linking molecular pathology to clinical care.
Castori M. Pain in Ehlers-Danlos syndromes: manifestations, therapeutic strategies and future perspectives. Expert Opin Orphan Drugs. 2016; 4(11):1145-1158 Article) Explores the manifestations, treatment options, and research gaps for pain in EDS, connecting symptom patterns to underlying biological mechanisms.
