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Epidural and subarachnoid administration of opioids for nonmalignant pain: Technical issues, current approaches and novel treatments
Epidural and Subarachnoid Adminisxation of Opioids for Nonmalignant Pain: Technical Issues, Current Approaches and Novel Treatments
Znhoductia Intraspinal opioid infusions are being offered to an increasing number of patients. especially those with chronic noncancer pain.‘*” With the application of implantrd infusion pumps and intrdspinal carheten to the noncancer setting. infusions are being given for periods of years and probably will continue for decade 10 come. The use of this modality in large numbcn of patients for very long time pr~iods ncressilatrs a considcndon
of the technical &sues ior the placement of thct pump and for the long-wrm management of [he hardware. There are areas in these rcchniral considerations thal are unclear and controversial. The% areas usually resuh from a lack of dclinirke informnrion about an operation arld hardwxc thal have been available, on a widespread basis, for only S-10 yrax Other considerations involve adherence to rhe proper techniqucs that are commonly acccptcd for the placement of an implanwd pump and inrrasp’nal cathewr. Thcsr trchniqun have been based upon iulormation gleaned from a large prxti-al cxpcricncc. Ignoring thcsr “minor” points, houewr. ran lead LO dicaruour pump complicatic,m or even a nonfunctional pump.
,More than simply awzssiny the tc~hni~al issues in the intrdspinal admi111s1m1ion of opioidn for ,,o,,malig1,a1,1 pain. there ~111: rendy we a nriety ol approaches 10 1hr 1,sc of 1hesc rerhniquer. AS cxpericnce with thrsf infusions is ncc1,mulatc~d. a,,d as rt,e li1rancinl rlimale in medicine changes, tllrse approaches conti,.,~! 10 chanxc. hur tx,haI’v toward a gcnerdl con~c1,sus. Reccn1 wic,,lifir adxancn. both in ncww analgeGr substancrr and in innovatwr Incthodr for i,,t:-aspinal delivery of rhcsc wh\?;tnres, also arr affcr1i1,g these approacho.
Conbvversial
or Unukar
Areas
Af,trr xn dpproprid1c pericd :)f wwnir,g infuGons. rhe ha\ic wxration co,,Gsl\ of 1hc placrmr,,r of a ~,1hru%meo,,s ~nlusion puml, that is conncc1ed 10 : I i,,,pla,,wd spi1nl cub eter. The ca1hctcr ca, bc located ii, 1he %pi,,al cpidural or inlrd1l,cc:ll space 31111is uswll) composed of silicon elaslomrr, allt,oi,gl, pollamide. nylon. an,:1 orhcr m;11erials arc often used. The pump is 11sually a progran,mablc pump [hat allows for adjuw,,cm ot flow ra1es and progzaamming for different ,aws ~11 diffcren1 timn of the 1!ay. This simple tlescr~prio,~ of rhr opcr~~io,,. howc~er. r&w5 several siynifca111 iswrs. Fo1 example. the me1hod for scree11ing is co,,1,0vcniat a1 the presen1 1imc. bccausc of 11,e different me1hods employed by different clinicians anti because of increasing preswres fro,,, rhird-party payors 10 wee,, padems on an 011~ pa1icnt basis. From a technical perspective. 1hr t)pc of carhew has raised srrong opinions based upon safcv and exe of we. Silicon clx1omcr is prohahly 1hc safest 1,,a1crhl for inwad,ccal placcmcn1 as irs use for I,,mboperi1oneal zhunts and vcntricu!opcri1onral sb1,,,1s I,a\ spanned a1 Iaxt three decades. 11 is, however, a difficult mawrial with which to work hecauw it is quite soft and pIiJhle and requires a s1m,cwhat larger wall rhicknus (and rcsuha111 larger ove1all outer diamewr). Sewer mawriids have a greater stiflness and lower surfxe cohesion, which allow a smaller 0u1rr diameter and Ixtter handling characteristics, hut decades of experience wit11 mos1 of 1bcsc materials don no1 exist. A recent conrrowny has developed with ucry-small-hwe cathctc,s.
alhou~h my toriciry might bc rlvtcd 10 rhc ,n,1wr of d,c ir,fu.ion rtwough thrse exrrr1:al r:ithrrtrr and 1l1e coiling of thr cathe1e1~ in 1hc ,,,0\1 i1,ft:rior arpec~s 111the 1hrcal sac. 7.” .Anstl,cl iw1c 1tu1 remdinr unrlear is 1bc approxl, for ti,e placemen of the spinal ~.~hetr~ :,1idli,,e or paramedian. The ,,,idl,r,e pl;,~,nc,,~ or tt,c \pii,al IICC~IIC and wbw q~wm c;l:hcvl- is clearly easier for most phyw cians. e\pec i.llly rw11r01,11’gc::,1~. There is PI?dc~llcc. ho\wwr, lt1;lt ;, wli c.,,t,erer (e.g., Gli101, ~1:1s1om~1) in a midline Iwd1ion ran he rucwe p*onv Lo mrrrmi11enr occlusion bawer,, chr spino11r p1orcrws. crperi.diy wi1h the spiuc in ex,rnio,,. ‘Tbc daily Ilrxion/rxlension r~~o~cmcn~~ of [lx spi1,c car, caurr the s[ ino1:s procr~\cs 10 impi11gc 11po1, 1hc -‘L~ler L.!,’ :x di\lodgr the cad,e1e1 ti01,, 1t.k ,i,:iaJI CJ~JI wide li1,w. Thr paramrdi.,,, approdct, lesse,1s, ho1 dots ,,1,1 climinxe, thrw problems. K’onerheless. the need for the larwr approach is do11lwd by many physicians who have used rhe midli1,c approach for Iargc numhen of parirnrs over a large period of 1irne v,irho1,1 Ggnifican1 problems. 13rr:~uw rhr pump and catheter arc p&cd 1r~ually a1 the sxnc lime. a dccuhi1us position is cmployrd I” 1he operadng room. Thir makrs the pxamrdian rpproxh more difticul1 because of the angle of rhr medic and tbr Y-IJI~ fluorowopic tube. Fo an anteroposterior x-my view. the ruhc u-2: nrrd 10 be nvar 1hc. exposed arca of *h.: hxk. will prcscm iwr1le d1aping challenga, and will lease,, the space near 11~. i,,cuio,,al a1ra in tbr back. II ,w1,ld seen, safe 10 SMIC tha, a progrx,,,. rnable infusion pump is the most common 1ype of pump being implanted today. A conrwn1-1x1~ inf1Gn pump can be suitable for caucer pdtieno. hu1 becomes unwieldy for long-1erm i,,,urions whew varying infusion rxcs a1 diifere,,! limes of I:W day and/o1 ch.mping raes owx 1imc (e.g.. monrhs 01 ycdn) are desired. Givc11 that the cost of a l”“gramn,ablc-r~1.c p1,mp is less than 50% g1~11cr dvn 3 rons1ant-r.ate pump. it is dilli~111110 we any berwlir 10 the 1,s~ of a co,,s1~,,1rate pump in noncancer pauenc, where a long-term infusion is contemplaled. Until recenrly, there KIS a co111rov~‘r~y concc1 ni,,g the cpid14 or inr,xhccal placcmc,,r of the ca1heter.““.“’ II, thr rxly years of longtern, in1raspinal i1,li,~io,,s. the F.uropear, cxpe-
\Shm placilrg lhe pump in lhe s”bc”tane. ous porkw iI is impwran! to develop the p”mp pockrt so tha, !be skin illc;Gon dll not lit over the injcrdwl par: of 0~ pump. The: pump III”,, not he placed 100 deep below the skin. 1 hesc: points fill avoid the problem: of having 10 ;x~r~~re the rrlill porr by paving dlc necdlc rhro”gh a flesh surgical incicion and harin~ the progr;mmm~g hca! not bc able 1” Icad 01’ pi-ogr?n, IllC pulnp. Adherc.irc ,,a r,.\nd;rrd recommc~~dcd ope~driie procrdurcs for pwnp placcmenr iurtudcs la) chcrkiny p”mp hmcfion brfore p”mp plxrmw:[. (h) initially filling the p”mp with only IO r”l. (rarhe: than 20 ml.) w pretent [he pamp from hcroming wcrpressurizcd rnd damaged. d-Id (ct securinp the pump 10 surro”ndting tissue hy wing the dacton pouch around die pump. Du6ng relills. iI is cxllrmely imporlant 10 ensure hat the correc, porr is injected. The ccn~c’r port is “red for retill ar;d the sideport is used for inrrapinal hoI”, injections. This rather ohviws biu ea,il) overlooked tmolot can bc liferaving.
Current Appronches Widl these wchnical cousiderrrions as a bari,. 111c current approach lo using for the pwbiblc pl:lrrmcnl of .3 permrncnr spinal inhrsion \pwm i9 10 “cc cithcr- multiple bolus i;ljcctionc or 3 short-ten m spinal infusion. Roth :qqxoxhes are widely wed. The former bccaurc of low COY, and owpadcnt “w. and Ihe Iacwr because of closer modeling 10 the final long-wrm inf”sion. The c”rrcm rrcnd. wi”g eilhcr wchnique, is for inurarhecal LCSing hcrd~~se of concerns from rome invcstigawrs cwr the ability of an epidural i?jcccion or inf”,ion 10 predict ~cc~:ratrly the s”cce% of a long-term in!rathec:l infwion. For long-term con~rot of nonnialignanl pai”, the currem trc”d is 10 rw long-lerm spinal infurions, will1 inrermiuenr bolus injection ~ystcms rcscrvcd for c~nccr pain control. Rcratw of rhe tong expected curvixal rimes for patierlts with nonmalignanr pain, Ihe impl.m,ed progmmnrahte p”mp is ~wd more commonly than Ihe CO~PLUN IXW inlusion pump hrca~~sc of rhr ftcxibiliry in adjwting dose raw wirh the ~“o~r.mmahle pump. \\%ilc tbe~ arr the current rrcnds. all of rhex area are and \\ill comin”e m be aflccred b, the
changing medical financial climale. crpe< ~:dh in managed care and cqwion. Thesr are r~ealing strong prcsures for ompatienl b&c tcsling and serious dc~dation~ of cm, not chqc. for vxioui medicatioru and delivery swems over lhc lifespan of the paiicnr. \$riour clinical inveslit:.1tom. including the present aurbor, are de.&q~ illg rconomic mod& for these CCJW and compi,,g the cow 1” other fcrrmr of Lrea”llCm IiN rverc nonmalignam pain.
NOVdWhile the inlraspinat infusions tor nomn *lignanl pain provide adequate pain relic f, rherc s a need for improved rnedwd~ of in!w oion that will 5pan decades. cspeci.llly in patienu wilt, ocurolxxhic pain. (:limc.d a Ed bait science rencarcb cfforw :II the prcv 111 time have focused upon newrr agctn~ atd novel delivery qstems fcr such agenw or naw rally ocrurring compounds. Nooopioid analgesics arc receiving cornidet-able aucntion a~ the prescm time hecdurc o1 the high incidence of neuropahic pdin in patienls with nonmalignant pain. The tirsr nonopioid analgesic agent 10 hc fully approved for intrapinal deliwry on a longterm basis appears to be ilonidine hydrorhloride. II is possible rhal mch a prepamtion, labeled for epidural use ;n terminally ill rancer paden&, might he a\-ai!dbtc wiithin I year, although this is deprndenr upon changing husincss consideraiom of one or IWO phzrmaceulical companies. Clonidinc hydrornlor& ha hcrn CXLIIIIincd in many published ivporu of intr+nal infusions in humans. xid more than 1500 patienu have been reported with intraspinA Irearment. The infusions hare hvx wed tot pain control during general aneslhcsia and for pain due 10 surgery, labor, canwr pain, nerw injury (c.g.. spinal cord ir$cry pain and limb slump pain), and clher nonmAignant conditions awxialed with chroair pain (arachnoiditis. low hack pain, epidurat $carring). Infornn lion presented at lhc .4lp!x-2 Adrenrrgic Mechanisms in Spiral Analgesia Symposium (Luccrae. Swiucrtand, .4ugw 17-10. lW3) indicated that Ihe most effcctivr- ux 01 cIo:>idine hydrochloride appear 10 be in the trrac. men, of neuroparhic pain. The doses for intrapinal infusion of ctonidinc hydrochloride have ranged from 25 ,o 900 ,,g
from ‘M LO 5 pg/hr (20-12’0 pg/day), with good !wxincd p:in relief tor a mc~n rollow-up of 14 IIIUI11!1\. Newer rcchmques for [be mtraspinal adminiswdtion of analgesic substance5 3150 are being cvaluatec’ h Gnple and less exprusive ahcrnarive ;s an implamed self-injection mul,icham ber ?3tem made ofsilzwic. The ~yxsrem conGts of a main reservoir with a volume 01 SO-50 mL thdr tills. at a known rate. a smzatlcr second chamber. which IS conrccwd 10 a spiel intrathecat catheter. The rnrire sys,cm i> implan,ed subcu~neously in the flank. rihcage, or abdominal awd. The patient can dcprcw the dome of the smaller chamber and ,hus give a boius inrrx thecal injection via the a,urhrd inrrxthcrat cahcrcr. The smaller chamber Ihen rctills ar a known rate from the main reservoir, rhns prw viding a “lock-out” timr when further dcprersion of ,hc dome of the smaller cham:Kr wilt not provide any furlher inuathecal injection. These invcsdgadonal sysrems rdise questions of the abitiry of the palicnt 10 rcliahty palpate and drprexs the dome of the smallrr chdmbcr, a$ well az the tong-term smhiliry of the !+srcm for frequent manipulation and refilling. Although such a s)swn is now being invesdgdred for cancer pain conrrut. it ir unclear whether this will be effcc,ivr for long-wrm (years or dccader) use in nonmalignant pain *rcdlmc‘llt. One of the mOS, i”“ln-dti\Y n1rhMts for analgcsic subsunce delivery is a rusuirwt-rrleuc ( rll matrix preparation for implantation ii1 the inlralhecdt +x~c”“* This mclhrwl is a, an invrsti~dtional IWIZI but involves Ihe retcwz of adornergir and chotinergic rompoundt from rhromaltin adrenal cetlr or aher cells tha, have tWC” gerxticdly mociifiert and have bee” implanud in rhe inuathccal space. Initial tcwb hxc hwn promising for sustiincd pain relief xithvut thr nerd for mrchcdliotl i”jecrio” into the imrdlhrral or epadurx, space.
Wiirh thr long-,wn USC of irmaspinal infw sions. wchnical icsucs can be xpam,ed into minor technical points and controvenial arex\ ,hnr sbffcr from tdck of ;tdqudtc information
Znhoductia Intraspinal opioid infusions are being offered to an increasing number of patients. especially those with chronic noncancer pain.‘*” With the application of implantrd infusion pumps and intrdspinal carheten to the noncancer setting. infusions are being given for periods of years and probably will continue for decade 10 come. The use of this modality in large numbcn of patients for very long time pr~iods ncressilatrs a considcndon
of the technical &sues ior the placement of thct pump and for the long-wrm management of [he hardware. There are areas in these rcchniral considerations thal are unclear and controversial. The% areas usually resuh from a lack of dclinirke informnrion about an operation arld hardwxc thal have been available, on a widespread basis, for only S-10 yrax Other considerations involve adherence to rhe proper techniqucs that are commonly acccptcd for the placement of an implanwd pump and inrrasp’nal cathewr. Thcsr trchniqun have been based upon iulormation gleaned from a large prxti-al cxpcricncc. Ignoring thcsr “minor” points, houewr. ran lead LO dicaruour pump complicatic,m or even a nonfunctional pump.
,More than simply awzssiny the tc~hni~al issues in the intrdspinal admi111s1m1ion of opioidn for ,,o,,malig1,a1,1 pain. there ~111: rendy we a nriety ol approaches 10 1hr 1,sc of 1hesc rerhniquer. AS cxpericnce with thrsf infusions is ncc1,mulatc~d. a,,d as rt,e li1rancinl rlimale in medicine changes, tllrse approaches conti,.,~! 10 chanxc. hur tx,haI’v toward a gcnerdl con~c1,sus. Reccn1 wic,,lifir adxancn. both in ncww analgeGr substancrr and in innovatwr Incthodr for i,,t:-aspinal delivery of rhcsc wh\?;tnres, also arr affcr1i1,g these approacho.
Conbvversial
or Unukar
Areas
Af,trr xn dpproprid1c pericd :)f wwnir,g infuGons. rhe ha\ic wxration co,,Gsl\ of 1hc placrmr,,r of a ~,1hru%meo,,s ~nlusion puml, that is conncc1ed 10 : I i,,,pla,,wd spi1nl cub eter. The ca1hctcr ca, bc located ii, 1he %pi,,al cpidural or inlrd1l,cc:ll space 31111is uswll) composed of silicon elaslomrr, allt,oi,gl, pollamide. nylon. an,:1 orhcr m;11erials arc often used. The pump is 11sually a progran,mablc pump [hat allows for adjuw,,cm ot flow ra1es and progzaamming for different ,aws ~11 diffcren1 timn of the 1!ay. This simple tlescr~prio,~ of rhr opcr~~io,,. howc~er. r&w5 several siynifca111 iswrs. Fo1 example. the me1hod for scree11ing is co,,1,0vcniat a1 the presen1 1imc. bccausc of 11,e different me1hods employed by different clinicians anti because of increasing preswres fro,,, rhird-party payors 10 wee,, padems on an 011~ pa1icnt basis. From a technical perspective. 1hr t)pc of carhew has raised srrong opinions based upon safcv and exe of we. Silicon clx1omcr is prohahly 1hc safest 1,,a1crhl for inwad,ccal placcmcn1 as irs use for I,,mboperi1oneal zhunts and vcntricu!opcri1onral sb1,,,1s I,a\ spanned a1 Iaxt three decades. 11 is, however, a difficult mawrial with which to work hecauw it is quite soft and pIiJhle and requires a s1m,cwhat larger wall rhicknus (and rcsuha111 larger ove1all outer diamewr). Sewer mawriids have a greater stiflness and lower surfxe cohesion, which allow a smaller 0u1rr diameter and Ixtter handling characteristics, hut decades of experience wit11 mos1 of 1bcsc materials don no1 exist. A recent conrrowny has developed with ucry-small-hwe cathctc,s.
alhou~h my toriciry might bc rlvtcd 10 rhc ,n,1wr of d,c ir,fu.ion rtwough thrse exrrr1:al r:ithrrtrr and 1l1e coiling of thr cathe1e1~ in 1hc ,,,0\1 i1,ft:rior arpec~s 111the 1hrcal sac. 7.” .Anstl,cl iw1c 1tu1 remdinr unrlear is 1bc approxl, for ti,e placemen of the spinal ~.~hetr~ :,1idli,,e or paramedian. The ,,,idl,r,e pl;,~,nc,,~ or tt,c \pii,al IICC~IIC and wbw q~wm c;l:hcvl- is clearly easier for most phyw cians. e\pec i.llly rw11r01,11’gc::,1~. There is PI?dc~llcc. ho\wwr, lt1;lt ;, wli c.,,t,erer (e.g., Gli101, ~1:1s1om~1) in a midline Iwd1ion ran he rucwe p*onv Lo mrrrmi11enr occlusion bawer,, chr spino11r p1orcrws. crperi.diy wi1h the spiuc in ex,rnio,,. ‘Tbc daily Ilrxion/rxlension r~~o~cmcn~~ of [lx spi1,c car, caurr the s[ ino1:s procr~\cs 10 impi11gc 11po1, 1hc -‘L~ler L.!,’ :x di\lodgr the cad,e1e1 ti01,, 1t.k ,i,:iaJI CJ~JI wide li1,w. Thr paramrdi.,,, approdct, lesse,1s, ho1 dots ,,1,1 climinxe, thrw problems. K’onerheless. the need for the larwr approach is do11lwd by many physicians who have used rhe midli1,c approach for Iargc numhen of parirnrs over a large period of 1irne v,irho1,1 Ggnifican1 problems. 13rr:~uw rhr pump and catheter arc p&cd 1r~ually a1 the sxnc lime. a dccuhi1us position is cmployrd I” 1he operadng room. Thir makrs the pxamrdian rpproxh more difticul1 because of the angle of rhr medic and tbr Y-IJI~ fluorowopic tube. Fo an anteroposterior x-my view. the ruhc u-2: nrrd 10 be nvar 1hc. exposed arca of *h.: hxk. will prcscm iwr1le d1aping challenga, and will lease,, the space near 11~. i,,cuio,,al a1ra in tbr back. II ,w1,ld seen, safe 10 SMIC tha, a progrx,,,. rnable infusion pump is the most common 1ype of pump being implanted today. A conrwn1-1x1~ inf1Gn pump can be suitable for caucer pdtieno. hu1 becomes unwieldy for long-1erm i,,,urions whew varying infusion rxcs a1 diifere,,! limes of I:W day and/o1 ch.mping raes owx 1imc (e.g.. monrhs 01 ycdn) are desired. Givc11 that the cost of a l”“gramn,ablc-r~1.c p1,mp is less than 50% g1~11cr dvn 3 rons1ant-r.ate pump. it is dilli~111110 we any berwlir 10 the 1,s~ of a co,,s1~,,1rate pump in noncancer pauenc, where a long-term infusion is contemplaled. Until recenrly, there KIS a co111rov~‘r~y concc1 ni,,g the cpid14 or inr,xhccal placcmc,,r of the ca1heter.““.“’ II, thr rxly years of longtern, in1raspinal i1,li,~io,,s. the F.uropear, cxpe-
\Shm placilrg lhe pump in lhe s”bc”tane. ous porkw iI is impwran! to develop the p”mp pockrt so tha, !be skin illc;Gon dll not lit over the injcrdwl par: of 0~ pump. The: pump III”,, not he placed 100 deep below the skin. 1 hesc: points fill avoid the problem: of having 10 ;x~r~~re the rrlill porr by paving dlc necdlc rhro”gh a flesh surgical incicion and harin~ the progr;mmm~g hca! not bc able 1” Icad 01’ pi-ogr?n, IllC pulnp. Adherc.irc ,,a r,.\nd;rrd recommc~~dcd ope~driie procrdurcs for pwnp placcmenr iurtudcs la) chcrkiny p”mp hmcfion brfore p”mp plxrmw:[. (h) initially filling the p”mp with only IO r”l. (rarhe: than 20 ml.) w pretent [he pamp from hcroming wcrpressurizcd rnd damaged. d-Id (ct securinp the pump 10 surro”ndting tissue hy wing the dacton pouch around die pump. Du6ng relills. iI is cxllrmely imporlant 10 ensure hat the correc, porr is injected. The ccn~c’r port is “red for retill ar;d the sideport is used for inrrapinal hoI”, injections. This rather ohviws biu ea,il) overlooked tmolot can bc liferaving.
Current Appronches Widl these wchnical cousiderrrions as a bari,. 111c current approach lo using for the pwbiblc pl:lrrmcnl of .3 permrncnr spinal inhrsion \pwm i9 10 “cc cithcr- multiple bolus i;ljcctionc or 3 short-ten m spinal infusion. Roth :qqxoxhes are widely wed. The former bccaurc of low COY, and owpadcnt “w. and Ihe Iacwr because of closer modeling 10 the final long-wrm inf”sion. The c”rrcm rrcnd. wi”g eilhcr wchnique, is for inurarhecal LCSing hcrd~~se of concerns from rome invcstigawrs cwr the ability of an epidural i?jcccion or inf”,ion 10 predict ~cc~:ratrly the s”cce% of a long-term in!rathec:l infwion. For long-term con~rot of nonnialignanl pai”, the currem trc”d is 10 rw long-lerm spinal infurions, will1 inrermiuenr bolus injection ~ystcms rcscrvcd for c~nccr pain control. Rcratw of rhe tong expected curvixal rimes for patierlts with nonmalignanr pain, Ihe impl.m,ed progmmnrahte p”mp is ~wd more commonly than Ihe CO~PLUN IXW inlusion pump hrca~~sc of rhr ftcxibiliry in adjwting dose raw wirh the ~“o~r.mmahle pump. \\%ilc tbe~ arr the current rrcnds. all of rhex area are and \\ill comin”e m be aflccred b, the
changing medical financial climale. crpe< ~:dh in managed care and cqwion. Thesr are r~ealing strong prcsures for ompatienl b&c tcsling and serious dc~dation~ of cm, not chqc. for vxioui medicatioru and delivery swems over lhc lifespan of the paiicnr. \$riour clinical inveslit:.1tom. including the present aurbor, are de.&q~ illg rconomic mod& for these CCJW and compi,,g the cow 1” other fcrrmr of Lrea”llCm IiN rverc nonmalignam pain.
NOVdWhile the inlraspinat infusions tor nomn *lignanl pain provide adequate pain relic f, rherc s a need for improved rnedwd~ of in!w oion that will 5pan decades. cspeci.llly in patienu wilt, ocurolxxhic pain. (:limc.d a Ed bait science rencarcb cfforw :II the prcv 111 time have focused upon newrr agctn~ atd novel delivery qstems fcr such agenw or naw rally ocrurring compounds. Nooopioid analgesics arc receiving cornidet-able aucntion a~ the prescm time hecdurc o1 the high incidence of neuropahic pdin in patienls with nonmalignant pain. The tirsr nonopioid analgesic agent 10 hc fully approved for intrapinal deliwry on a longterm basis appears to be ilonidine hydrorhloride. II is possible rhal mch a prepamtion, labeled for epidural use ;n terminally ill rancer paden&, might he a\-ai!dbtc wiithin I year, although this is deprndenr upon changing husincss consideraiom of one or IWO phzrmaceulical companies. Clonidinc hydrornlor& ha hcrn CXLIIIIincd in many published ivporu of intr+nal infusions in humans. xid more than 1500 patienu have been reported with intraspinA Irearment. The infusions hare hvx wed tot pain control during general aneslhcsia and for pain due 10 surgery, labor, canwr pain, nerw injury (c.g.. spinal cord ir$cry pain and limb slump pain), and clher nonmAignant conditions awxialed with chroair pain (arachnoiditis. low hack pain, epidurat $carring). Infornn lion presented at lhc .4lp!x-2 Adrenrrgic Mechanisms in Spiral Analgesia Symposium (Luccrae. Swiucrtand, .4ugw 17-10. lW3) indicated that Ihe most effcctivr- ux 01 cIo:>idine hydrochloride appear 10 be in the trrac. men, of neuroparhic pain. The doses for intrapinal infusion of ctonidinc hydrochloride have ranged from 25 ,o 900 ,,g
from ‘M LO 5 pg/hr (20-12’0 pg/day), with good !wxincd p:in relief tor a mc~n rollow-up of 14 IIIUI11!1\. Newer rcchmques for [be mtraspinal adminiswdtion of analgesic substance5 3150 are being cvaluatec’ h Gnple and less exprusive ahcrnarive ;s an implamed self-injection mul,icham ber ?3tem made ofsilzwic. The ~yxsrem conGts of a main reservoir with a volume 01 SO-50 mL thdr tills. at a known rate. a smzatlcr second chamber. which IS conrccwd 10 a spiel intrathecat catheter. The rnrire sys,cm i> implan,ed subcu~neously in the flank. rihcage, or abdominal awd. The patient can dcprcw the dome of the smaller chamber and ,hus give a boius inrrx thecal injection via the a,urhrd inrrxthcrat cahcrcr. The smaller chamber Ihen rctills ar a known rate from the main reservoir, rhns prw viding a “lock-out” timr when further dcprersion of ,hc dome of the smaller cham:Kr wilt not provide any furlher inuathecal injection. These invcsdgadonal sysrems rdise questions of the abitiry of the palicnt 10 rcliahty palpate and drprexs the dome of the smallrr chdmbcr, a$ well az the tong-term smhiliry of the !+srcm for frequent manipulation and refilling. Although such a s)swn is now being invesdgdred for cancer pain conrrut. it ir unclear whether this will be effcc,ivr for long-wrm (years or dccader) use in nonmalignant pain *rcdlmc‘llt. One of the mOS, i”“ln-dti\Y n1rhMts for analgcsic subsunce delivery is a rusuirwt-rrleuc ( rll matrix preparation for implantation ii1 the inlralhecdt +x~c”“* This mclhrwl is a, an invrsti~dtional IWIZI but involves Ihe retcwz of adornergir and chotinergic rompoundt from rhromaltin adrenal cetlr or aher cells tha, have tWC” gerxticdly mociifiert and have bee” implanud in rhe inuathccal space. Initial tcwb hxc hwn promising for sustiincd pain relief xithvut thr nerd for mrchcdliotl i”jecrio” into the imrdlhrral or epadurx, space.
Wiirh thr long-,wn USC of irmaspinal infw sions. wchnical icsucs can be xpam,ed into minor technical points and controvenial arex\ ,hnr sbffcr from tdck of ;tdqudtc information