Long-lasting Epidural Sensory Blockade by n-Butyl-p-Aminobenzoate in the Terminally Ill Intractable Cancer Pain Patient

Korsten, H.H.M.; Ackerman, E. W.; Grouls, R. J. E.; Zundert, André van; Boon, Willem; Bal, Filiz; Crommelin, M. A.; Ribot, J. G.; Hoefsloot, F.; Slooff, J. L.

doi:10.1097/00000542-199112000-00005

Cited by 38 publications

(9 citation statements)

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“…Anesthetics injected into the epidural space diffuse across the nerve sheaths surrounding the dorsal roots, thereby gaining access to the underlying sensory nerve fibers. Clinical studies have demonstrated that the epidural administration of hydrophobic suspensions of n-butyl-p-aminobenzoate (BAB), a butyl ester of aminobenzoic acid, produces long-duration analgesia (Ͼ30 days) in patients suffering from chronic pain (Shulman et al, 1990(Shulman et al, , 1998Korsten et al, 1991). This long-lasting anesthesia is thought to result from the slow, sustained release of BAB from the suspension onto the dorsal root.…”

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confidence: 99%

Inhibition of the A-Type K+ Channels of Dorsal Root Ganglion Neurons by the Long-Duration Anesthetic Butamben

Winkelman¹,

Beck²,

Ypey³

et al. 2005

The Journal of Pharmacology and Experimental Therapeutics

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n-Butyl-p-aminobenzoate (BAB; butamben) is a long-duration anesthetic used for the treatment of chronic pain. Epidural administration of BAB is thought to reduce the electrical excitability of dorsal root nociceptor fibers by inhibiting voltagegated ion channels. To further investigate this mechanism, we examined the effects of BAB on the potassium currents of acutely dissociated neurons from the rat dorsal root ganglion (DRG). These neurons express a rapidly inactivating A-type K ϩ current (I A ) that is resistant to tetraethylammonium (20 mM) but inhibited by 4-aminopyridine (5 mM). At low concentrations, BAB (Յ1 M) selectively inhibited the I A component of DRG K ϩ current. The voltage dependence of activation and inactivation, kinetics of recovery from inactivation, and the pharmacology of the DRG I A were similar to those of the Kv4 family of K ϩ channels. Reverse transcription-polymerase chain reaction was used to establish that the messages encoding for all three of the mammalian Kv4 channel subunits (Kv4.1-Kv4.3) were present in the rat DRG. BAB produced a high-affinity, partial inhibition of heterologously expressed Kv4.2 channels (K D ϭ 59 nM) but did not alter the kinetics or voltage sensitivity of gating. Substituting polar threonines for conserved hydrophobic residues of the S6 segment weakened BAB binding but did not alter the voltage-dependent gating of the Kv4.2 channel. At physiological pH, BAB is uncharged, suggesting that hydrophobic interactions may contribute to drug binding. The data support a mechanism in which BAB binds near the narrow cytoplasmic entrance of Kv4 channels and inhibits current by a pore blocking mechanism.

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Inhibition of the A-Type K+ Channels of Dorsal Root Ganglion Neurons by the Long-Duration Anesthetic Butamben

Winkelman¹,

Beck²,

Ypey³

et al. 2005

The Journal of Pharmacology and Experimental Therapeutics

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“…5,6 Investigations during the early 1990s examined alternative carriers and delivery vehicles to extend local anesthetic duration 7 but generally met with limited success. These included biodegradable surgical implants, 8 various lipid-based solutions, suspensions and emulsions, [9][10][11] and alterations of pH. 12 Recent interest in the long-acting local anesthetic properties of antidepressant drugs has been tempered by concerns regarding neurotoxicity.…”

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confidence: 99%

Extended-Duration Analgesia: Update on Microspheres and Liposomes

Rose

Neal

Kopacz

2005

Regional Anesthesia and Pain Medicine

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“…A promising new approach for the management of chronic pain is the epidural administration of sustained release formulations of local anesthetics. For example, epidural injections of the local anesthetic n-butyl-p-aminobenzoate (BAB) have proved to be effective in treating the intractable pain associated with advanced stages of cancer (Korsten et al, 1991;Shulman et al, 1998). A single epidural treatment with BAB can effectively relieve chronic pain for prolonged intervals (Ͼ30 days).…”

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confidence: 99%

“…A single epidural treatment with BAB can effectively relieve chronic pain for prolonged intervals (Ͼ30 days). Surprisingly, the pain relief produced by BAB is not associated with any demonstrable loss of motor function, suggesting that BAB selectively targets the nociceptive nerve fibers of the dorsal root (Korsten et al, 1991;Shulman et al, 1998;McCarthy et al, 2002). Because BAB is hydrophobic and uncharged at physiological pH, it partitions into lipid bilayers but does not effectively distribute into the systemic circulation (Shulman et al, 1998;Kuroda et al, 2000).…”

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confidence: 99%

“…Because BAB is hydrophobic and uncharged at physiological pH, it partitions into lipid bilayers but does not effectively distribute into the systemic circulation (Shulman et al, 1998;Kuroda et al, 2000). The analgesia produced by BAB is highly localized with no detectable anesthesia in adjacent spinal segments (Korsten et al, 1991;Grouls et al, 2000). The absence of significant side effects coupled with the long-duration anesthesia provides considerable support for the use of BAB formulations in the treatment of chronic pain.…”

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Kv1.1 Channels of Dorsal Root Ganglion Neurons Are Inhibited by n-Butyl-p-aminobenzoate, a Promising Anesthetic for the Treatment of Chronic Pain

Beekwilder¹,

O’Leary²,

Broek³

et al. 2003

The Journal of Pharmacology and Experimental Therapeutics

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In this study, we investigated the effects of the local anesthetic n-butyl-p-aminobenzoate (BAB) on the delayed rectifier potassium current of cultured dorsal root ganglion (DRG) neurons using the patch-clamp technique. The majority of the K ϩ current of small DRG neurons rapidly activates and slowly inactivates at depolarized voltages. BAB inhibited the whole-cell K ϩ current of these neurons with an IC 50 value of 228 M. Dendrotoxin K (DTX K ), a specific inhibitor of Kv1

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Long-lasting Epidural Sensory Blockade by n-Butyl-p-Aminobenzoate in the Terminally Ill Intractable Cancer Pain Patient

Cited by 38 publications

References 0 publications

Inhibition of the A-Type K+ Channels of Dorsal Root Ganglion Neurons by the Long-Duration Anesthetic Butamben

Inhibition of the A-Type K+ Channels of Dorsal Root Ganglion Neurons by the Long-Duration Anesthetic Butamben

Extended-Duration Analgesia: Update on Microspheres and Liposomes

Kv1.1 Channels of Dorsal Root Ganglion Neurons Are Inhibited by n-Butyl-p-aminobenzoate, a Promising Anesthetic for the Treatment of Chronic Pain

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