Therapeutic Protocol For Pudendal Nerve Inflammation / Chronic Pelvic Pain

• Once a correct diagnosis and cause (etiopathogenesis) of the disease has been established, our therapeutic protocol will involve:

• At the first line, systemic muscle relaxants (BACLOFEN) and local relaxants (DILATAN) for the perineal muscles, combined with benzodiazepines (CLONAZEPAM) and contact anti-inflammatory agents (cortisone enemas).
• The second line of therapy will involve neuromodulators (Amitriptyline, Pregabalin, and Duloxetine).
• The third line will consist of corticosteroid and anesthetic infiltrations in the Alcock canal.
• The fourth line, which involves surgical decompression to release the entrapped nerve, is reserved for the most severe cases (usually trauma sequelae).

FIRST LINE: BACLOFEN

We use Baclofen to alleviate symptoms associated with excessive contraction of the pelvic floor muscles; it has a muscle-relaxing and antispasmodic effect, acting on GABA receptors at the central nervous system level.
Effects of Baclofen on Perineal Spasms

• Muscle Relaxation:
  • Reduces the hypertonicity of the pelvic floor muscles, improving the relaxation of the muscles involved in the spasm.
  • It is useful for conditions such as Chronic Pelvic Pain Syndrome (CPPS), where perineal spasms contribute to the pain.
• Analgesic Effect:
  • Through muscle relaxation, Baclofen can reduce nerve compression and improve circulation, thereby alleviating pain associated with spasms.
•  Reduction of Reflex Contractions:
  • Decreases the reactivity of neuromuscular circuits, preventing involuntary reflex contractions that often characterize this condition.

FIRST LINE: CLONAZEPAM

Clonazepam is a benzodiazepine primarily used as an anticonvulsant and anxiolytic. In our protocol, it is employed off-label due to its effects on the central and peripheral nervous systems.

Effects of Clonazepam on Chronic Pelvic Pain

1. Reduction of Muscle Contracture:
   • Clonazepam has a muscle-relaxing effect, useful for reducing the hypertonicity of the pelvic floor muscles, which often contributes to chronic pelvic pain.
   • This can be particularly beneficial in cases where the pain is associated with muscle spasms or pelvic floor dysfunctions.
2. Sedative and Anxiolytic Effect:
   • By reducing anxiety and promoting overall relaxation, clonazepam can help decrease the perception of pain, which is often amplified by emotional tension and chronic stress.
3. Neuropathic Pain Modulation:
   • Clonazepam acts on GABA-A receptors, inhibiting neuronal hyperactivity. This makes it useful in situations where pelvic pain has a neuropathic component, such as pudendal neuralgia or other nerve-related pelvic floor disorders
4. Regulation of Central Pain Circuits:
   • By modulating the central nervous system, the drug can help “desensitize” pain pathways, improving the quality of life for patients suffering from chronic pelvic pain.

SECOND LINE: AMITRIPTYLINE

The three mechanisms of action of amitriptyline

1.  Effects on Calcium and Potassium Channels
2. Amitriptyline affects calcium and potassium channels, which are involved in the transmission of pain signals from the periphery to the central nervous system, as well as in pain sensitization. Several studies have shown that the number of calcium channels increases under neuropathic pain conditions, potentially leading to aberrant pain transmission. This drug can enhance the activity of descending inhibitory pain pathways and activate interneurons that directly release pain-inhibitory substances, such as endogenous opioids (D. Fornasari).
   Effects on Calcium Channels
3. By reducing calcium influx into neurons, Amitriptyline limits the release of excitatory neurotransmitters such as glutamate and substance P, contributing to the reduction of central sensitization—a phenomenon that amplifies pain in conditions like neuropathy or fibromyalgia. Additionally, by acting on presynaptic terminals, inhibition of calcium channels decreases excessive pain signal release, attenuating pain pathway activation both from the periphery to the center and vice versa.
4. Amitriptyline also influences potassium channels, which regulate neuronal excitability. This can contribute to pain control and stabilization of the neuronal membrane. It can enhance potassium channels (specifically inward-rectifier potassium channels), which are essential for maintaining the balance and function of excitable cells. By stabilizing the membrane potential, it renders cells less excitable and reduces pain transmission. Furthermore, hyperpolarization of sensory neurons helps to suppress persistent pain signals.

1. Reduction of Abnormal Activity in Sensory Neurons
   o Amitriptyline reduces abnormal activity in sensory neurons, which often plays a significant role in neuropathic pain.
2. Sedative Properties
   o Amitriptyline has sedative properties that improve sleep quality, a critical factor for patients with chronic pain. Better sleep can reduce pain perception and enhance overall patient resilience.

SECOND LINE: PREGABALIN

The five mechanisms of action of pregabalin:

Pregabalin is an anticonvulsant and analgesic medication commonly used to treat neuropathic pain and as an adjunctive therapy in epileptic seizures. Its mechanism of action, like that of amitriptyline, primarily involves inhibiting abnormal nerve transmission through interaction with specific calcium channels. Pregabalin acts predominantly by binding to the subunits of voltage-gated calcium channels, particularly in neurons of the central and peripheral nervous systems. These subunits are crucial for regulating calcium influx into neurons, a process that is essential for the release of neurotransmitters involved in pain transmission.

1. Selective binding to calcium channel subunits (α2δ): By binding selectively to these subunits, Pregabalin reduces calcium influx into neurons, which in turn decreases the release of excitatory pain neurotransmitters, such as glutamate and substance P. The ultimate effect is the modulation of pain signals along neural pathways.
2. Reduction of abnormal neuronal circuit activation: By lowering calcium influx, Pregabalin limits central sensitization, a common phenomenon in chronic neuropathic pain.
3. Reduction of long-term potentiation of pain (LTP): The decreased calcium influx also helps reduce LTP, a process that amplifies pain signals in the spinal cord.
4. Peripheral nerve modulation: In damaged peripheral nerves, Pregabalin exerts a modulatory effect by reducing neuronal excitability and abnormal impulse transmission, ultimately improving neuropathic pain symptoms.
5. Indirect GABAergic effects: Although Pregabalin does not directly interact with GABA receptors (whose inhibitory action helps maintain the balance between excitation and inhibition), its use can increase GABA levels in certain areas of the brain, promoting an indirect calming effect on the central nervous system.

SECOND LINE: DULOXETINE

Finally, for hygienists and nature lovers, I am making a list of natural anti-inflammatory substances for completeness:

• Aloe vera, a natural ally against inflammation.
• Mallow: help from nature.
• Devil’s claw against inflammation.
• Natural anti-inflammatory: spirea.
• White willow to relieve inflammation.
• Ginseng or ginger to fight inflammation.