Chronic Pain — Factors That Keep Pain Persistent (Often Overlooked)

Most readers benefit from reviewing this Quick Summary together with the sections on Diagnosis of the True Cause of Pain, Mechanical Factors, Metabolic and Nutritional Factors, and Treatment Approach. The following sections provide a detailed explanation of how these factors interact and how they can be addressed in a structured and individualized way.

Why Treatment Fails in Chronic Pain — What Is Actually Missed in Diagnosis and Treatment

In many patients, treatment fails not because the condition is untreatable, but because the pain is not precisely analyzed at three critical levels.

First, the exact anatomical structure responsible for the pain is often not identified. Pain may be attributed to findings seen on imaging, while the true source — such as joints, ligaments, muscles, fascia, or nerves — remains unrecognized.

Second, even when the correct structure is suspected, the specific pathological process within that structure is not clearly defined. Inflammation, mechanical irritation, instability, micro-injury, or nerve sensitization require different treatments, yet therapy is often applied without this distinction.

Third, contributing factors that continue to provoke and maintain pain are frequently overlooked. These include mechanical overload, repetitive strain, asymmetrical loading, and poor movement patterns, but also chronic low-grade inflammation, metabolic factors (such as insulin resistance), nutritional influences, and altered tissue recovery capacity. Because these processes remain active, they can continuously trigger pain even when the primary condition is being treated.

Because of this, treatment may appear correct but remains incomplete, which is why pain persists or returns.

For this reason, when treatment does not work, the key step is not repeating the same approach, but performing a structured reassessment — identifying the exact structure involved, the process within it, and all relevant contributing factors that sustain the pain.

This is why chronic pain is often misunderstood and incorrectly treated in everyday clinical practice. It may appear as low back pain, nerve pain (neuralgia), post-surgical pain, or widespread pain syndromes such as fibromyalgia. Although these conditions seem different, they are often driven by similar underlying mechanisms.

Most patients are given a “diagnosis” that is often just the name of a syndrome (such as trigeminal neuralgia or low back pain). This describes where the pain is or how it behaves, but does not explain its true cause. A true diagnosis would identify the underlying problem — for example, not just low back pain, but inflammation at the attachment of specific posterior ligaments of the sacroiliac joint. At the same time, imaging findings are often presented as the cause, even though many of these changes are incidental and not responsible for the patient’s symptoms. In the same patient with low back pain, if imaging shows degenerative disc changes, these are often assumed to be the cause without detailed clinical evaluation, even though they may simply be age-related findings, especially in older patients. Even when a specific ligament inflammation is identified as the source of pain, it is essential to detect the systemic contributing factors that promote the onset and persistence of the pain syndrome (e.g., improper sitting posture, pro-inflammatory diet, metabolic disturbances, etc.).

Identifying which of these factors are dominant in an individual patient is often not straightforward and usually requires structured clinical analysis, as multiple factors frequently coexist and interact. This applies to most chronic pain syndromes, including conditions such as interstitial cystitis, occipital neuralgia, pudendal neuralgia, intercostal neuralgia, postherpetic neuralgia, low back pain, Tarlov cyst and neck pain where different mechanisms may overlap and lead to incomplete or ineffective treatment.

This page explains the local and contributing mechanisms that can cause pain to persist and lead to unsuccessful treatment when they are not properly identified.

Organizational and system-related reasons why pain treatment may fail — such as limited consultation time, protocol-based therapy, or lack of follow-up — are explained here: Understanding why pain treatment may fail in real clinical practice

Image: Different types of back pain

Chronic Pain Has a Local Source — Even When It Is Not Visible on Images

In most cases, pain begins in a specific structure such as:

• joint
• ligament
• muscle
• fascia
• peripheral nerve

This structure is called the pain generator.

What Is Actually Happening in These Tissues

Pain is rarely caused by a single process.

In most cases, it develops through a combination of:

• inflammation
• micro-injury / repetitive strain
• muscle spasm
• fascial tension
• nerve irritation or micro-compression

Here are 2 examples of the combination of different processes developing in tissues.

1) Fascia — the invisible source of pain

Fascia (connective tissue) is one of the most common sources of chronic pain.

It can:

• become tight
• lose elasticity
• develop trigger points

And importantly, it is not visible on standard imaging.

2) Nerve irritation without clear damage

Nerves may be affected in very small compression zones:

• without major structural compression
• without clear MRI findings

This leads to persistent pain signals despite “normal” imaging.

Central Sensitization — Why Pain Becomes Persistent

Over time, continuous pain signals lead to changes in the nervous system. This process is called central sensitization, often described as the “wind-up” phenomenon.

With repeated stimulation, the nervous system becomes increasingly reactive:

• minor stimuli produce stronger pain
• normally non-painful sensations may become painful
• pain persists even after the initial cause is reduced

This is one of the key reasons why chronic pain behaves differently from acute pain. A similar mechanism of central sensitization is often seen in conditions such as fibromyalgia.

Treatment may include:

• explanation of pain mechanisms
• appropriate medication when needed
• gradual exposure to movement
• reduction of fear and avoidance patterns

This is particularly important in long-lasting pain.

Diagnosis of the True Cause of Pain

In many patients, the true pain generator is not clearly visible on MRI or CT scans. At the same time, imaging may show abnormalities that are incidental, age-related, and not responsible for symptoms.

Because of this, establishing a correct diagnosis requires a detailed understanding of pain anatomy—that is, knowing which specific structures can produce pain in a given syndrome (such as low back pain, trigeminal neuralgia, or neck pain) and how to confirm their involvement.

In clinical practice, physical examination is often more important than imaging. The key is to analyze:

• the characteristics of pain
• what triggers it
• what reduces or worsens it

and to perform targeted tests that increase or decrease pain, helping to identify the true source.

These assessments can be performed not only in person, but also during video consultations. In many cases, the relevant information is already present in the medical documentation patients provide, or can be recognized through guided testing during the consultation—although patients are often not aware of its importance.

This is one of the main reasons why pain can persist for a long time despite treatment: the underlying cause has not been precisely identified, and therapy is therefore not directed at the true pain generator.

Treatment Begins With Identifying the True Source of Pain

Once the pain generator is identified, treatment becomes significantly more effective.

Medication strategy

Treatment usually starts with carefully selected combinations of medications, adjusted gradually over time.

This is particularly important in patients who:

• already had procedures
• underwent surgery
• did not improve with standard therapy

Very often, the problem is not that “nothing works,” but that the treatment was not targeted to the real source of pain

Advanced options

If needed, additional methods may be used:

• nerve blocks
• radiofrequency ablation
• neuromodulation
• surgery

Chronic Pain Is Not Only a Local Problem

One of the most important facts is that chronic pain is almost never caused by a single factor

Instead, it persists because multiple systems interact at the same time, including:

• mechanical load and daily habits
• muscle and fascial tension
• nerve sensitivity and autonomic nervous system activity
• metabolic and inflammatory factors
• nutritional status and pro-inflammatory diet
• tissue quality and regeneration capacity
• sleep, circadian rhythm, and hormonal regulation
• gut–brain interactions
• psychological and emotional factors
• cumulative stress on the body over time

These factors do not act independently — they often reinforce each other, creating a persistent pain cycle.

Mechanical Overload and Daily Habits as Contributing Factors to Chronic Pain

Chronic pain is very often maintained by continuous mechanical stress. Common examples include:

• prolonged sitting — most often affecting the lumbosacral region and neck
• long periods in fixed positions (standing or sitting without movement)
• repetitive lifting or carrying loads (especially with poor technique)
• repetitive movements (typing, using a mouse, manual work, sports which can cause irritation of the ulnar nerve at the wrist, or elbow, or the median nerve)
• prolonged computer or smartphone use (forward head posture, shoulder strain)
• asymmetrical postures (leaning to one side, crossing legs compressing the perineal nerve, carrying a bag on one shoulder, or a tight belt in meralgia )
• sleeping in poor positions (improper pillow or mattress support)
• sudden increase in physical activity (unprepared tissues exposed to higher load)
• Altered gait patterns due to anomalies (leg length discrepancy) or joint diseases, such as those affecting the hip, knee, or ankle.

High-risk groups

Certain professions are particularly exposed:

• working at a computer for many hours daily
• professional musicians (neck, shoulder, wrist overload)
• office workers
• manual laborers
• athletes with repetitive movements

Over time, this leads to:

• chronic overload of fascia, ligaments, muscles, and joints
• micro-injuries from repeated strain
• local inflammation
• slower tissue recovery
• muscle fatigue and persistent muscle spasm
• reduced flexibility of soft tissues
• joint irritation
• nerve irritation, micro-compression, and sensitization- Thoracic outlet syndrome, or pain after nerve injury

Importantly, these factors can be corrected only after identifying which specific structure is generating pain, what process is occurring within it, and how to reduce or relieve the load on that exact tissue. Once this is identified, it is necessary to carefully analyze the situations in which mechanical load occurs, in order to understand how to relieve stress on the painful structures. Different patients with low back pain do not require the same type of unloading.

For example:

• if pain comes from posterior ligaments of the sacroiliac joint, prolonged sitting and certain movements may need to be modified, sometimes with the use of cushions, new chair or positional adjustments
• if the problem is cervical muscle and fascial overload, computer posture and head position need to be corrected
• if pain is related to repetitive wrist or forearm strain, hand positioning and activity patterns must be adjusted
• if a peripheral nerve is irritated, even small positional changes may significantly reduce symptoms

Metabolic and Inflammatory Factors as Contributing Factors to Chronic Pain

Certain systemic conditions can significantly influence pain:

• insulin resistance
• excess visceral fat and adipokine activity
• elevated uric acid
• chronic low-grade inflammation
• excess body weight (increased mechanical and inflammatory load)
• hormonal imbalance (especially thyroid dysfunction and altered cortisol regulation)

These factors:

• increase pain sensitivity
• slow tissue recovery
• reduce treatment effectiveness

Because of this, in chronic pain, basic laboratory evaluation is often necessary, including:

• fasting glucose
• fasting insulin
• HbA1c
• glucose and insulin response after a glucose load (when indicated)
• lipid profile
• thyroid function tests
• inflammatory markers
• uric acid levels

When these abnormalities are identified, targeted correction can significantly improve pain control, especially when combined with treatment directed at the actual pain source.

Nutritional Deficiencies as Contributing Factors to Chronic Pain

Deficiencies in key nutrients can directly affect pain:

• vitamin B12 — nerve dysfunction and neuropathic pain
• vitamin D — musculoskeletal pain, weakness, and reduced recovery
• magnesium — muscle tension, cramps, and increased excitability
• iron — fatigue and reduced muscle performance
• vitamin B1 (thiamine) — nerve dysfunction, especially in metabolic and alcohol-related conditions
• vitamin B6 — both deficiency and excess may contribute to neuropathic symptoms

Even mild deficiencies may contribute to persistent symptoms. In many patients, these deficiencies are not recognized without appropriate testing.

Evaluation may include:

• vitamin B12 levels
• vitamin D levels
• magnesium levels
• iron status
• selected B vitamins when clinically indicated

Correction may include:

• targeted supplementation
• dietary adjustments
• follow-up monitoring

However, supplementation alone is usually not sufficient unless the underlying cause of pain is also identified and treated.

These deficiencies do not act in isolation — they often coexist with metabolic and inflammatory factors, further increasing pain sensitivity and slowing recovery.

Diet and Its Role in Chronic Pain

Diet does not only affect nutrient levels — it also directly influences inflammation, metabolism, and pain sensitivity.

In many patients, dietary habits contribute to the persistence of pain, especially when metabolic disturbances such as insulin resistance or chronic low-grade inflammation are already present.

Common contributing patterns include:

• high intake of processed foods and refined carbohydrates
• excessive sugar consumption
• frequent spikes in blood glucose and insulin levels
• imbalance between pro-inflammatory and anti-inflammatory nutrients
• irregular eating patterns and long periods without proper meals

These factors may:

• increase systemic inflammation
• worsen metabolic imbalance
• increase pain sensitivity
• slow tissue recovery

Importantly, even foods generally considered healthy may have negative effects when consumed in inappropriate amounts or in the wrong metabolic context. For example, fruit contains important nutrients and antioxidants, but high intake of sugars may worsen glucose regulation in patients with insulin resistance, indirectly contributing to inflammation and persistence of pain.

Similarly, diets that appear “balanced” may still promote inflammation if they:

• contain excessive refined carbohydrates
• lack sufficient protein
• include poor-quality fats

Because of this, evaluating diet is not about following a universal plan, but about understanding how specific eating patterns affect the individual patient.

Dietary changes can significantly improve pain control, but only when they are aligned with:

• the patient’s metabolic state
• the underlying pain mechanism
• other contributing factors such as mechanical load and nervous system sensitization

For this reason, diet should always be considered as part of a comprehensive approach to chronic pain, rather than as an isolated solution.

Obesity and Its Role in Chronic Pain

Obesity influences chronic pain through multiple interacting mechanisms.

On a mechanical level, excess body weight increases load on joints, ligaments, and the spine, particularly in:

• the lumbosacral region
• hips and knees
• feet

This leads to:

• faster tissue overload
• joint irritation
• earlier muscle fatigue

However, obesity is not only a mechanical problem.

Adipose tissue is metabolically active and produces substances (adipokines) that contribute to:

• chronic low-grade inflammation
• increased pain sensitivity
• slower tissue healing

Because of this, obesity is closely linked with:

• insulin resistance
• metabolic imbalance

Another important factor is reduced physical conditioning.

Many patients with chronic pain decrease their activity over time, which leads to:

• loss of muscle strength
• reduced endurance
• decreased joint and spine stability

This creates a cycle:

pain → reduced activity → deconditioning → more pain

For these reasons, obesity should be understood as a combined mechanical, metabolic, and functional factor in chronic pain. Obesity can contribute to the development and persistence of chronic pain. At the same time, chronic pain often reduces mobility and physical activity, which can lead to weight gain.

This creates a cycle:

pain → reduced movement → weight gain → increased load and inflammation → more pain

Because of this, simply advising patients to lose weight, without first reducing pain and enabling movement, is often not realistic or effective.

A combined approach is usually necessary, where pain is addressed first to allow gradual return to activity, which then supports sustainable weight reduction.

Tissue Quality and Regeneration

Not all tissues recover equally.

Factors such as:

• reduced blood flow
• degeneration
• repeated micro-injuries

lead to:

• slower healing
• increased vulnerability to pain

In many patients, additional factors further impair tissue recovery, such as:

• persistent mechanical overload
• age-related changes in tissue structure
• chronic low-grade inflammation
• inadequate nutrition (e.g., vitamin D deficiency)

When these factors are present, treatment directed only at symptoms is often not sufficient.

Medications may temporarily reduce pain, but they usually cannot provide significant or lasting improvement unless the underlying conditions affecting tissue recovery are also addressed.

Sleep, Circadian Rhythm, and Hormonal Regulation

Sleep quality and circadian rhythm play an important role in how pain is processed.

Poor or disrupted sleep can:

• increase pain sensitivity
• reduce pain tolerance
• impair tissue recovery

Hormonal regulation, particularly cortisol rhythm, also influences inflammation and pain perception.

Because of this, sleep is not usually the primary cause of pain, but it can significantly amplify existing pain and slow recovery.

Autonomic Nervous System as a Contributing Factor to Chronic Pain

The autonomic nervous system plays a major role in chronic pain. In some patients, increased sympathetic activity maintains pain.

This may lead to:

• temperature changes
• altered circulation
• increased sensitivity

This mechanism is especially important in:

• sympathetically maintained pain
• CRPS (complex regional pain syndrome)

Gut–Brain Axis as a Contributing Factor to Chronic Pain

The gastrointestinal system can influence pain through several mechanisms, particularly in patients with metabolic or inflammatory disturbances.

Relevant factors include:

• altered gut motility (constipation, irregular bowel function)
• changes in gut microbiota composition (dysbiosis)
• increased intestinal permeability
• chronic low-grade inflammation originating from the gut

These changes may:

• contribute to systemic inflammation
• affect nervous system sensitivity
• influence how pain is perceived and maintained

In clinical practice, this is more relevant in patients who also have:

• bloating or abdominal discomfort
• irregular bowel movements
• food intolerances
• symptoms consistent with irritable bowel syndrome

Addressing these factors may support overall pain management, but they are rarely the primary cause of chronic pain.

Treatment approaches may include:

• dietary adjustments
• correction of nutritional deficiencies
• management of bowel function
• in selected cases, modulation of gut microbiota (e.g., probiotics or prebiotics), although evidence remains variable

The goal is not to “treat the gut instead of pain,” but to reduce contributing systemic factors that may amplify pain.

Psychological and Emotional Factors as Contributing Factors to Chronic Pain

Psychological factors do not mean that pain is imaginary. Pain is a real biological process, but it is also influenced by how the nervous system processes and amplifies signals.

In many patients, persistent pain leads to changes in the nervous system, a process known as central sensitization.

Over time, this may result in:

• increased sensitivity to pain
• stronger response to minor stimuli
• persistence of pain even when the original cause is reduced

Emotional and psychological factors interact with this process.

Important factors include:

• chronic stress
• anxiety
• depression

It is often assumed that depression causes pain. In reality, the opposite is frequently true — long-lasting pain leads to psychological distress, which then further amplifies pain and makes treatment more difficult.

These factors can:

• lower pain threshold
• increase muscle tension
• maintain a cycle of pain → stress → more pain

Because of this, psychological factors are not the primary cause of pain, but they can significantly influence its intensity, persistence, and response to treatment.

Treatment of depressive and anxiety-related factors in chronic pain involves a combination of pharmacological and non-pharmacological approaches. In clinical practice, antidepressants are often used, as they can reduce the perception of pain by acting on central pain-processing mechanisms, in addition to improving mood. Psychotherapy plays an important role, helping patients better understand and manage their responses to pain.

Support from family and close social environment is also a significant factor, as it reduces the feeling of isolation and improves motivation for treatment. In some individuals, spiritual aspects (such as religion) may have a positive effect, as well as relaxation techniques, including breathing exercises and gradual return to daily activities.

However, this approach is often overemphasized in practice, especially when the true anatomical source of pain has not been clearly identified. In such cases, treatment may remain incomplete, as it addresses the consequences rather than the underlying cause.

Cumulative Stress on the Body (Allostatic Load)

Chronic pain is rarely caused by a single event.

It often develops after years of:

• physical strain
• poor sleep
• metabolic imbalance
• psychological stress

This cumulative burden is called allostatic load.

It reduces the body’s ability to regulate pain effectively.

Medications and Previous Treatments That May Contribute to Pain

Chronic pain may sometimes be influenced or maintained by medications or previous treatments. This is often overlooked.

Certain drugs can affect:

• muscle function
• nerve sensitivity
• metabolic balance
• inflammatory processes

Common examples include:

• statins — may contribute to muscle pain, weakness, or increased muscle sensitivity
• some antidepressants — may alter pain perception or cause fatigue
• long-term use of certain pain medications — may lead to reduced effectiveness or increased sensitivity (medication overuse or hyperalgesia)
• corticosteroids — may affect metabolism, muscle tissue, and recovery
• sedative medications — may reduce physical activity and worsen deconditioning
• vitamin B6 (pyridoxine) excess — prolonged high intake (often through supplements) may lead to sensory neuropathy, tingling, or burning pain; both deficiency and excess can affect nerve function

Previous treatments may also play a role:

• surgery (scar tissue, altered biomechanics, nerve irritation), similar to postdiscectomy pain, pain after surgery of internal organs, pain after lumbar or cervical spine surgery
• repeated injections
• incomplete or misdirected rehabilitation programs

In many patients, these factors do not directly cause pain, but they may:

• maintain or amplify existing pain
• interfere with recovery
• reduce the effectiveness of otherwise appropriate treatment

Because of this, a detailed review of all medications and previous treatments is an important part of evaluation.

In some cases, modifying or adjusting therapy may significantly improve symptoms.

Other Medical Conditions That May Contribute to Pain

Chronic pain is sometimes influenced by other medical conditions that are not directly related to the primary pain source.

These conditions may:

• increase pain sensitivity
• slow recovery
• reduce treatment effectiveness

Common contributing conditions include:

• diabetes and insulin resistance — affecting nerve function and healing
• thyroid disorders — influencing metabolism and muscle function
• chronic inflammatory conditions
• autoimmune diseases
• anemia and chronic fatigue states
• hormonal imbalances
• sleep disorders

In some patients, these conditions are already diagnosed but not considered relevant to pain.

In others, they remain unrecognized.

These factors rarely act as the sole cause of pain, but they often:

• maintain symptoms
• make pain more persistent
• reduce response to treatment

Because of this, identifying and addressing these conditions is an important part of a comprehensive approach to chronic pain.

Why Treatments Do Not Work the Same for Everyone

Not all patients respond equally to the same therapy.

One important reason is genetic variability in drug metabolism.

This explains why some patients feel that “nothing helps” despite appropriate treatment

How Chronic Pain Is Actually Treated

Effective treatment of chronic pain is not possible unless both are identified and addressed:

• the primary pain generator
• the factors that contribute to and maintain the pain

Treatment must target both levels simultaneously.

Anti-Inflammatory Diet and Nutritional Strategy

In many patients, diet directly contributes to the persistence of pain, especially when metabolic disturbances are present.

Treatment includes:

• implementation of an anti-inflammatory diet
• reduction of refined carbohydrates and sugars
• stabilization of glucose and insulin levels
• adequate protein intake
• improvement of fat quality
• individualized adjustment based on metabolic status

An anti-inflammatory diet is not a universal plan, but a structured approach adapted to:

• insulin sensitivity
• level of inflammation
• body composition
• type of pain

Even foods considered healthy, such as fruit, may contribute to metabolic imbalance when consumed in excess, particularly in patients with insulin resistance.

Dietary intervention can significantly improve pain control, but only when combined with treatment of the underlying pain mechanism.

Manual Therapy and Osteopathic Approaches

Manual therapy techniques, including osteopathic treatment, are often used in patients with chronic pain, particularly when dysfunction involves muscles, fascia, joints, or movement patterns.

These approaches may include:

• mobilization of joints
• soft tissue and fascial techniques
• muscle relaxation methods
• correction of movement patterns

In selected patients, such techniques can reduce local tissue tension, improve mobility, and temporarily decrease pain.

However, their effectiveness depends on whether the actual pain generator has been correctly identified.

Limitations of Osteopathic and Manual Therapy Approaches

In many patients with chronic pain, manual therapy alone is not sufficient.

This is particularly true when:

• the primary pain source is not correctly identified
• mechanical overload persists in daily activities
• metabolic or inflammatory factors are present
• central sensitization has developed

In such cases, manual therapy may provide only temporary relief without addressing the underlying mechanism of pain.

Because of this, these methods should be considered as part of a broader, individualized treatment strategy, rather than a standalone solution.

Key Takeaway

Chronic pain is not caused by a single problem.

It is the result of interaction between:

• a local pain source
• mechanical stress and daily habits
• metabolic, nutritional, and inflammatory factors
• nervous system changes (including central sensitization)
• psychological and functional factors

Effective treatment begins only when all of these are identified and addressed together, in a coordinated and individualized way. However, in clinical practice, there is often an excessive focus on a single contributing factor. These factors are not present in all patients, and even when they are, addressing them alone is usually insufficient without first identifying and treating the primary pain-generating structure.

Frequently Asked Questions About Chronic Pain and Its Causes