PCOL 7-2 Chronic Pain

Chronic Pain and Neuropathic Pain

• Chronic pain is defined as persistent pain lasting more than three months, affecting daily activities and quality of life.
• Neuropathic pain can be caused by conditions such as diabetes, nerve injury, or infections affecting the nervous system.

Hyperalgesia

• Hyperalgesia refers to an increased sensitivity to pain, resulting in exaggerated responses to noxious stimuli.

Induction of Inflammatory Pain

• Inflammatory pain in animal models is typically induced using agents such as complete Freund's adjuvant or carrageenan.

Measuring Pain Responses

• Von Frey filaments measure mechanical thresholds to evaluate nociceptive (pain-related) responses in animal models.

Opioid Use Effects

• Potential effects of chronic opioid use NOT seen include enhancing immune function.

Primary Afferents After Damage

• Surviving primary afferents following partial damage may exhibit increased excitability and sensitivity.

Opioids in Chronic Pain Management

• Opioids are characterized by their ability to produce pain relief but may lead to tolerance and dependence.

Voltage-Gated Calcium Channels (VGCC)

• N-type VGCCs are predominantly found in the central presynaptic terminals of afferents entering the spinal cord.

VGCC Blockers

• Blockers derived from cone-snail toxins are classified as selective for N-type VGCCs, demonstrating potential for pain management.

GABA Analogues in Neuropathic Pain

• GABA analogues, such as gabapentin and pregabalin, work by inhibiting excitatory neurotransmitter release, thereby modulating pain pathways.

Best Practice for Neuropathic Pain

• Current best practice approaches include a combination of pharmacotherapy, physical therapy, and psychological support tailored to individual needs.

Side Effects of GABA Analogues

• Common side effects of GABA analogues may include dizziness, sedation, and weight gain.

Antidepressants and Pain Management

• Tricyclic antidepressants, including amitriptyline and nortriptyline, are often used to manage chronic pain and neuropathic pain effectively.

Targeted Neurotransmitters

• Antidepressants primarily target neurotransmitters such as serotonin and norepinephrine to enhance mood and alleviate pain.

Mixed Receptors in Antidepressants

• Some antidepressants exhibit mixed actions at receptors such as serotonin (5-HT) and norepinephrine transporters.

Mood and Pain Connection

• Serotonin is a key neurotransmitter involved in mood modulation, which can influence pain perception.

Capsaicin Mechanism

• Topical TRPV1 agonists like capsaicin act by desensitizing nociceptive neurons, ultimately reducing pain transmission.

Function of TRPV1 Receptors

• TRPV1 receptors are involved in sensing pain and temperature changes, playing a vital role in nociception.

First-Line Treatment for Neuropathic Pain

• Treatments not classified as first-line options typically include opioids and complex analgesics, replaced by safer alternatives.

Gabapentin and Pregabalin Mechanism

• Gabapentin and pregabalin primarily act by inhibiting the release of excitatory neurotransmitters through the modulation of VGCCs.

Chronic Pain Treated with Capsaicin

• Topical capsaicin can effectively treat neuropathic pain conditions, such as diabetic neuropathy and postherpetic neuralgia.

Second-Line Treatments for Neuropathic Pain

• Antidepressants and anticonvulsants are often considered second-line treatments when first-line approaches fail or are inadequate.