When I was in school science class, I was taught that nerves under the skin sensed pain, such as touching a hot stove, and sent the signal to the brain, which then sent back a signal to react, like pulling the hand away. But that’s not the way it happens.

“We don’t have pain receptors,” explains neuroscientist pain specialist Lorimer Moseley. Pain comes not from the region feeling it, but from the brain’s evaluation of danger from the senses, expectations, previous exposure, cultural/social norms/beliefs, and how we feel about these. Pain, as defined by the International Association for the Study of Pain, is “an unpleasant sensory and emotional experience associated with actual or potential tissue damage.” Pain is a localized emotion.

Does that mean it’s all in our heads? No-“danger detectors” distributed across body tissues act as the eyes of the brain. So here’s what happens.

Nociceptive pain (meaning in response to stimuli) is an early warning. Nerves have sensed temperature, vibration, stretching, oxygen starvation, or chemical changes from damaged cells, and send an early warning to the brain, which in turn starts the inflammatory response, protecting the area and sending in neutrophils to fight any infection, widening narrow blood vessels to increase blood flow and volume (causing swelling and redness).

But there are two problems. First, the inflammatory response also increases pain sensitivity-yes, that means you feel pain more intensely than you did before the injury, an over-reaction. And second, the mitochondria (the organelle responsible for cell digestion and respiration) spilled from damaged cells are attacked by the neutrophils as invaders-setting up a needless second round of inflammatory response (and you guessed it-more pain sensitivity). In chronic pain, the true need for the pain is distorted, and the pain self-perpetuating.

The cause of the signals can be confusing as well. In somatic pain, the pain is sharp, localized, and hurts to touch. But visceral pain is a vague, deep ache, hard to localize-such as cramps or colic. Problems in the pelvis, abdomen, or thorax can manifest as lower, middle, or upper back pain, respectively. Pain can also be referred, such as a heart attack felt in the shoulders, back, or neck, rather than the chest.

To address pain caused by acute injury, turn off the danger detectors. This can mean medically treating the underlying cause, like antibiotics for an infection. When the brain feels it’s safe, the pain will stop. Analgesics can be used to block the signals and hence the pain-but now we’re back to the problems of taking these long term. Codeine, for example, can even increase pain sensitivity. And all analgesics can cause analgesic rebound, where the body’s production of natural endorphins drops in response to analgesic use, increasing sensitivity to pain once again.

Non-nociceptive pain is another whole world. Here there’s no outside stimulus, as the signal is coming from within the nervous system itself, whether between the nerves between the tissues and the spinal cord (peripheral nervous system) or between the spinal cord and the brain (central nervous system). The cause could be nerve degeneration (as in stroke, multiple sclerosis, or oxygen starvation), a trapped nerve (under pressure or a disc problem), nerve infection (such as shingles), a nerve injury (from a fracture or soft tissue injury) – all signals misinterpreted as pain.

This sympathetic pain can be intense, to prevent use, which in turn causes new problems, like muscle wasting, osteoporosis, and stiffness in the joints (the new collagen is stiffer than the replaced collagen). It can even be pathological pain, an abnormal, amplified, malfunctioning, dysfunctional pain that includes fibromyalgia, irritable bowel syndrome, and some headaches.

Neuropathic pain is responsible for both phantom limb pain, from mild “pins and needles” to a constant and severe burning sensation, and for the extreme limb pain of complex regional pain syndrome after a seemingly small tissue insult like an insect bite or a minor cut. But once pain becomes chronic, in conditions like lower back pain, rheumatoid arthritis, fibromyalgia or cancer pain, treatment becomes elusive.

Pain not associated with an acute injury could be from any of a variety of factors: immune system, endocrine system, movement issues, cognition, or the very mechanisms by which the brain represents the body. Sensitivity increases, the dark side of neuroplasticity. Negative emotions increase the pain, such as sadness, anxiety, dwelling on the pain, or simply poor job satisfaction. Negative emotions are the result of chronic pain as well-depression is common in chronic pain sufferers.

Muscle knots, awkward posture, Vitamin D deficiency, bisphosphonates (for osteoporosis or Paget’s disease), and statins (for lowering high cholesterol) can all cause pain. Even an easy to identify complaint such as back pain could be due to poor posture, bad lifting, overweight (hard on the knees too), curved spine, traumatic injury, high heels, poor mattress, poor shoes, aging/degeneration of the spine, disease (rheumatoid arthritis, osteoarthritis, fibromyalgia, gallbladder, cancer, multiple sclerosis, stomach ulcers, AIDS), psychological factors following physical healing… it’s complex.

So after your doctor has addressed the acute injury and offered analgesics if appropriate, imagine the immense and confusing task if the pain persists. So doctors and their patients try things: massage, TENS units, anticonvulsants, antidepressants, acupuncture, meditation, chiropractic, osteopaths, biofeedback, low impact exercise, stretching, physical therapy, cognitive behavior therapy – fact is, they’re doing their best, but they’re guessing.

“We don’t have enough evidence from studies to know just which approach is right for which patient,” acknowledges Dr. Russell Porteny, chair of pain medicine at Beth Israel Hospital and past president of the American Pain Society. “Despite decades of research,” notes WebMD, “chronic pain remains poorly understood and notoriously hard to control. A survey by the American Academy of Pain Medicine found that even comprehensive treatment… helps, on average, only about 58% of people with chronic pain.” And even that means managing pain, not curing it.

Pain and pain response varies from person to person, and with the same person moment to moment. “Any credible evidence that the body is in danger and protective behavior would be helpful will increase the likelihood and intensity of pain,” explains Dr. Moseley. “Any credible evidence that the body is safe will decrease the likelihood and intensity of pain.

“It is as simple and as difficult as that.”