Comprehensive List of Pain Relievers Throughout Medical History
The evidence provided does not contain a complete historical catalog of every analgesic ever developed, but I can synthesize from the available guidelines and research to provide you with the major categories and specific agents documented in pain medicine history.
Primary Analgesics
Non-Opioid Analgesics (WHO Step I)
Based on established guidelines, these foundational agents include 1:
NSAIDs (Nonsteroidal Anti-Inflammatory Drugs):
- Acetylsalicylic acid (aspirin) - developed ~1860s
- Ibuprofen
- Ketoprofen
- Diclofenac
- Naproxen
- Mefenamic acid
- Celecoxib (COX-2 selective inhibitor)
Simple Analgesics:
- Acetaminophen (paracetamol) - in use since 1890s 2
- Acetanilide (forerunner of acetaminophen) - discovered ~130 years ago 3
- Phenazone - discovered ~130 years ago 3
Weak Opioids (WHO Step II)
1:
- Codeine
- Tramadol
- Dihydrocodeine
Strong Opioids (WHO Step III)
Oral morphine remains the gold standard first-choice opioid for moderate-to-severe cancer pain 1. The complete list includes 1:
- Morphine
- Methadone
- Oxycodone
- Hydromorphone
- Fentanyl (including transmucosal and transdermal formulations)
- Alfentanyl
- Buprenorphine (transdermal)
- Heroin
- Levorphanol
- Oxymorphone
Adjuvant Analgesics
These drugs were originally developed for other indications but have proven analgesic properties 4:
Antidepressants
Preferred agents for older adults include duloxetine, desipramine, and nortriptyline 4:
Tricyclic Antidepressants (TCAs):
- Amitriptyline
- Imipramine
- Nortriptyline (secondary amine - better tolerated)
- Desipramine (secondary amine - better tolerated)
SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors):
- Duloxetine (30-120 mg daily)
- Venlafaxine (75-225 mg daily)
- Milnacipran
Other Antidepressants:
- Bupropion (150-450 mg daily)
- SSRIs (sertraline, citalopram, escitalopram, paroxetine, fluoxetine, fluvoxamine)
Anticonvulsants
For neuropathic pain, gabapentinoids are first-line alongside antidepressants 4, 5:
Alpha-2-Delta Calcium Channel Antagonists:
- Gabapentin (900-3600 mg daily in divided doses)
- Pregabalin (up to 600 mg daily in divided doses)
Sodium Channel Antagonists/Membrane Stabilizers:
- Various anticonvulsants with efficacy in non-cancer neuropathic pain 6
Topical Agents
Topical analgesics should be considered whenever pain is focal or regional 4:
- Lidocaine patch 5%
- Diclofenac gel
- Diclofenac patch (180 mg)
- Capsaicin
- Ketamine (topical)
- Salicylate topicals
Alpha-2 Adrenergic Agonists
4:
- Tizanidine
- Clonidine
Muscle Relaxants
- Cyclobenzaprine (shown benefit for fibromyalgia)
- Baclofen (GABA agonist)
- Various skeletal muscle relaxants (though not preferred for chronic pain 4)
NMDA Receptor Antagonists
- Ketamine
- Memantine
- Dextromethorphan
Corticosteroids
5:
- Various glucocorticoids for bone pain and bowel obstruction-related pain
Cannabinoids
4:
- Medicinal cannabinoids (various formulations)
Neuroleptics
4:
- Selected antipsychotic agents with analgesic properties
Other Specialized Agents
4:
- Botulinum toxin injection
- Osteoclast inhibitors (for bone pain)
- Antisecretory drugs (for bowel obstruction pain)
- Ziconotide (intrathecal infusions for refractory chronic pain) 7
Emerging and Investigational Agents
- Nerve growth factor antagonists
- Tumor necrosis factor inhibitors
- Chemokine antagonists or neutralizing antibodies
- TRPV1 antagonists
- P2X purinergic receptor blockers
- Various heterocyclic scaffolds under investigation (azoles, pyrazoles, indoles, imidazoles, benzimidazoles, triazoles, oxazoles, thiazoles, oxadiazoles, thiadiazoles)
Historical Context
The earliest documented pain treatments date back to 3000 BC using naturally occurring plant materials 2. The modern era of pain medicine began with:
- Salicylic acid synthesis (1860) 2
- Pyrazolone group/antipyrine (1883) 2
- Phenacetin (1886) 2
- Acetaminophen (1890s) 2
- Morphine isolation and general/local anesthesia (19th century) 11
Important Caveats
The evidence emphasizes that most adjuvant analgesics are centrally acting and must be used cautiously, particularly in older adults 4. Treatment should always be initiated at low doses with gradual titration, and ineffective drugs should be discontinued promptly.
For neuropathic pain specifically, the preferred approach combines an analgesic antidepressant or gabapentinoid with concurrent topical agents when appropriate 4.
This list represents the major documented analgesic agents but is not exhaustive of every compound ever investigated, as comprehensive historical catalogs were not provided in the evidence base.