Ziconotide Tablet

Neuropathic pain is a chronic ache condition caused by lesions or diseases of the somatosensory nervous system. Its pathogenesis is complex, and clinical manifestations commonly include burning, stabbing, and electric‑shock‑like ache, which severely impair patients' quality of life. Severe neuropathic ache encompasses various subtypes, such as postherpetic neuralgia (PHN), painful diabetic peripheral neuropathy, central ache following spinal cord injury, central post‑stroke ache, radiculopathy, and refractory ache associated with spinal stenosis.

Such ache responds poorly to conventional analgesics (e.g., nonsteroidal anti‑inflammatory drugs, opioids), and patients often face challenges including poorly controlled ache and poor tolerability of adverse reactions. As a novel non‑opioid analgesic with a unique mechanism of action, ziconotide tablet provides a new therapeutic option for severe neuropathic ache.

2.1 Application in Postherpetic Neuralgia (PHN)

Postherpetic neuralgia (PHN) is the most common complication of herpes zoster, defined as severe neuropathic ache that persists or recurs in the affected area for more than 3 months after rash resolution. It severely disrupts patients' sleep, mood, and daily activities. The pathogenesis of PHN is primarily related to nerve injury, neuroinflammation, and central sensitization following varicella‑zoster virus infection. Conventional medications (e.g., gabapentin, pregabalin, opioids) yield unsatisfactory outcomes in some patients, especially elderly individuals or those with comorbidities, who often experience poor tolerability of adverse effects and inadequate pain control.

By blocking N‑type calcium channels in the dorsal horn of the spinal cord, it inhibits ache signal transmission and effectively relieves symptoms such as burning and stabbing ache in PHN patients. A 12‑week multicenter randomized controlled trial demonstrated that in patients with moderate‑to‑severe PHN refractory to conventional analgesics, treatment with it resulted in a significant reduction in visual analogue scale (VAS) ache scores compared with baseline, with a ache relief rate exceeding 60%, along with marked improvements in sleep quality and emotional state.

2.2 Application in Painful Diabetic Peripheral Neuropathy

Painful diabetic peripheral neuropathy is one of the most common chronic complications of diabetes and belongs to peripheral neuropathic ache. It mainly presents as symmetric ache in the distal extremities (e.g., hands and feet), accompanied by numbness, hypoesthesia, and burning sensations. Ache severity worsens progressively with disease progression, severely compromising patients' quality of life. Its pathogenesis involves nerve metabolic disturbances, oxidative stress, neuroinflammation, and nerve fiber damage induced by chronic hyperglycemia.

Conventional management focuses on glycemic control, neurotrophic therapy, and the use of anticonvulsants, antidepressants, and opioids. However, ache control is suboptimal in some patients, and long‑term opioid use carries risks of tolerance and dependence.

Targeting the pathogenesis of painful diabetic peripheral neuropathy, it blocks N‑type calcium channels to suppress ache signal transmission, thereby effectively alleviating extremity ache. A clinical study enrolling 200 patients with moderate‑to‑severe painful diabetic peripheral neuropathy showed that 8 weeks of ziconotide tablet treatment significantly reduced VAS scores, with a ache relief rate of 58.5%, and also partially improved paresthesia and numbness.

2.3 Application in Central Pain Following Spinal Cord Injury

Central ache following spinal cord injury is a common complication of spinal cord injury and a subtype of central neuropathic ache. It manifests as persistent or paroxysmal ache below the level of injury, typically described as burning, electric‑shock‑like, or numbness ache. It is severe, poorly responsive to conventional analgesics, and severely impairs rehabilitation and quality of life. Its pathogenesis is mainly associated with central nervous system remodeling, neurotransmitter imbalance, central sensitization, and overactivation of N‑type calcium channels after spinal cord injury, representing a clinically challenging form of neuropathic ache.

As an N‑type calcium channel blocker, it is an important agent for central ache following spinal cord injury. Multiple clinical studies have confirmed its efficacy in relieving ache and improving quality of life in affected patients. A cohort study included 20 patients with central ache following spinal cord injury refractory to standard pharmacotherapy, who received test intrathecal snx111 (clinical data for oral tablets may be extrapolated from intrathecal administration).

Ache scores decreased by more than 40% in 14 patients, and 11 underwent permanent pump implantation. After a mean follow‑up of 3.59 years, 8 patients maintained pain scores below threshold levels, with baseline VAS scores decreasing from 7.91 to 4.31 at the last follow‑up and a mean daily dose of 7.2 μg, without significant long‑term adverse events. Furthermore, it does not interfere with motor function recovery or exacerbate nerve injury in spinal cord injury patients, supporting its long‑term use.

2.5 Application in Refractory Pain Associated with Radiculopathy and Spinal Stenosis

Refractory ache related to radiculopathy and spinal stenosis is a common chronic neuropathic ache condition caused by nerve root compression, inflammation, or injury. It presents with radiating extremity ache, numbness, weakness, and severe ache intensity. Conventional treatments (e.g., nonsteroidal anti‑inflammatory drugs, physical therapy, nerve root blocks) often yield unsatisfactory results, and some patients require surgery yet may still experience residual ache, severely impairing quality of life.

Its pathogenesis is associated with nerve root edema, inflammatory responses, abnormal neurotransmitter release, and N‑type calcium channel activation following compression.As a potent non‑opioid analgesic, it effectively relieves ache in patients with refractory radiculopathy‑ and spinal stenosis‑related ache, offering a new therapeutic option for those intolerant to or unresponsive to surgery. Clinical studies show that it treatment significantly alleviates radiating ache and numbness, reduces VAS scores by more than 40% from baseline, and provides long‑lasting ache relief, improving patients' ability to perform daily activities. Unlike opioids, it does not induce tolerance, dependence, constipation, or respiratory depression, supporting long‑term administration. Furthermore, combination with nerve root block therapy produces synergistic analgesia, reducing the frequency of blocks and treatment costs.